Imidazopyridine-derivatives as inducible no-synthase inhibitors

ABSTRACT

The compounds of formula (I) 
     
       
         
         
             
             
         
       
     
     In which R1, R2, R3, R4, R5 and A have the meanings as given in the description are novel effective iNOS inhibitors.

FIELD OF APPLICATION OF THE INVENTION

The invention relates to novel imidazopyridine derivatives, which areused in the pharmaceutical industry for the production of pharmaceuticalcompositions.

KNOWN TECHNICAL BACKGROUND

In the German Patent Application DE 2504252 and in the European PatentApplication EP 0125756 3H-imidazo[4,5-b]pyridine derivatives withanti-ulcer activity are described.

The International Application WO 0049015 describes pyridine compoundswith inhibitory activity on the production of nitric oxide.

DESCRIPTION OF THE INVENTION

It has now been found that the novel aminosulphonylphenyl-substitutedimidazopyridine derivatives, which are described in greater detailsbelow, have surprising and particularly advantageous properties.

The invention thus relates, in a first embodiment (embodiment a), tocompounds of formula I

in which

-   R1 is hydrogen or 1-4C-alkyl,-   R2 is hydrogen or 1-4C-alkyl, and-   R3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantly    fluorine-substituted 1-4C-alkoxy;-   or in which-   R1 is 3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/or    R12-substituted phenyl, in which-   R11 is 1-4C-alkyl, halogen, 1-4C-alkoxy, or mono- or    di-1-4C-alkylamino,-   R12 is 1-4C-alkyl or halogen,-   R2 is hydrogen, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or    1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl,    or completely or predominantly fluorine-substituted 1-4C-alkoxy;-   or in which-   R1 and R2 together and with inclusion of the nitrogen atom, to which    they are bonded, form a heterocyclic ring Het, in which-   Het is a fully saturated or partially unsaturated mono- or fused    bicyclic ring or ring system made up of    -   a first constituent being a 3- to 7-membered monocyclic fully        saturated non-aromatic heterocyclic ring B,        -   which heterocyclic ring B comprises one to three heteroatoms            independently selected from nitrogen, oxygen and sulfur,        -   and which heterocyclic ring B is optionally substituted by            one or two oxo groups,

and, optionally, fused to said first constituent,

-   -   a second constituent being a benzene ring,    -   and which ring Het is optionally substituted by R21 on a ring        carbon atom,    -   and/or which ring Het is optionally substituted by R22 on a        further ring carbon atom,    -   and/or which ring Het is optionally substituted by an        ethylenedioxy group,    -   and/or which ring Het is optionally substituted by R23 on a ring        nitrogen atom,    -   in which

-   R21 is 1-4C-alkyl, 1-4C-alkoxy or phenylcarbonyl,

-   R22 is 1-4C-alkyl or 1-4C-alkoxy,

-   R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,    1-4C-alkoxy-2-4C-alkyl, mono- or di-1-4C-alkylamino-2-4C-alkyl,    phenyl, pyrimidyl, pyridyl, formyl, 3-7C-cycloalkyl,    3-7C-cycloalkylmethyl, or R231- and/or R232-substituted phenyl, in    which

-   R231 is halogen, cyano or 1-4C-alkyl,

-   R232 is halogen or 1-4C-alkyl, and

-   R3 is hydrogen, halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl,    or completely or predominantly fluorine-substituted 1-4C-alkoxy;

-   and in which

-   R4 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy,

-   R5 is 1-4C-alkyl,

-   A is 1-4C-alkylene;

-   the salts, N-oxides and the salts of the N-oxides of these    compounds.

The invention relates, in a second embodiment (embodiment b), tocompounds of formula I, in which

-   R1 is hydrogen or 1-4C-alkyl,-   R2 is hydrogen or 1-4C-alkyl, and-   R3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantly    fluorine-substituted 1-4C-alkoxy;-   or in which-   R1 is 3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/or    R12-substituted phenyl, in which-   R11 is 1-4C-alkyl, halogen, 1-4C-alkoxy, or mono- or    di-1-4C-alkylamino,-   R12 is 1-4C-alkyl or halogen,-   R2 is hydrogen, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or    1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl,    or completely or predominantly fluorine-substituted 1-4C-alkoxy;-   or in which-   R1 and R2 together and with inclusion of the nitrogen atom, to which    they are bonded, form a heterocyclic ring Het, in which-   Het is a 3- to 10-membered saturated or partially saturated    heterocyclic ring comprising totally 1 to 3 heteroatoms selected    from a group consisting of oxygen, sulfur and nitrogen, and    optionally substituted by R21 on a ring carbon atom and/or by R22 on    a further ring carbon atom and/or by R23 on a ring nitrogen atom, in    which-   R21 is 1-4C-alkyl, 1-4C-alkoxy or phenylcarbonyl,-   R22 is 1-4C-alkyl or 1-4C-alkoxy,-   R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,    1-4C-alkoxy-2-4C-alkyl, mono- or di-1-4C-alkylamino-2-4C-alkyl,    phenyl, pyrimidyl, pyridyl, formyl, 3-7C-cycloalkyl,    3-7C-cycloalkylmethyl, or R231- and/or R232-substituted phenyl, in    which-   R231 is halogen, cyano or 1-4C-alkyl,-   R232 is halogen or 1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl,    or completely or predominantly fluorine-substituted 1-4C-alkoxy;-   and in which-   R4 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy,-   R5 is 1-4C-alkyl,-   A is 1-4C-alkylene;-   the salts, N-oxides and the salts of the N-oxides of these    compounds.

1-4C-Alkyl is a straight-chain or branched alkyl radical having 1 to 4carbon atoms. Examples are the butyl, isobutyl, sec-butyl, tert-butyl,propyl, isopropyl, and, particularly, the ethyl and methyl radicals.

2-4C-Alkyl is a straight-chain or branched alkyl radical having 2 to 4carbon atoms. Examples are the butyl, isobutyl, sec-butyl, tert-butyl,propyl, isopropyl and, particularly, ethyl radical.

1-4C-Alkylene is a straight chain alkylene radical having 1 to 4 carbonatoms. Examples which may be mentioned in this context are the methylene(—CH₂—), ethylene (—CH₂—CH₂—), trimethylene (—CH₂—CH₂—CH₂—) and thetetramethylene (—CH₂—CH₂—CH₂—CH₂—) radical.

1-4C-Alkoxy is a radical which, in addition to the oxygen atom, containsa straight-chain or branched alkyl radical having 1 to 4 carbon atoms.Alkoxy radicals having 1 to 4 carbon atoms which may be mentioned inthis context are, for example, the butoxy, isobutoxy, sec-butoxy,tert-butoxy, propoxy, isopropoxy, and, particularly, the ethoxy andmethoxy radicals.

3-7C-Cycloalkyl stands for cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl and cycloheptyl, of which cyclopropyl, cyclobutyl andcyclopentyl are preferred.

3-7C-Cycloalkylmethyl stands for a methyl radical, which is substitutedby one of the above-mentioned 3-7C-cycloalkyl radicals. Examples whichmay be mentioned are the cyclopropylmethyl and the cyclohexylmethylradicals.

Halogen within the meaning of the present invention is bromine, orpreferably chlorine or fluorine.

Completely or predominantly fluorine-substituted 1-4C-alkoxy is, forexample, the 2,2,3,3,3-pentafluoropropoxy, the perfluoroethoxy, the1,2,2-trifluoroethoxy and in particular the 1,1,2,2-tetrafluoroethoxy,the 2,2,2-trifluoroethoxy, the trifluoromethoxy and the difluoromethoxyradical, of which the difluoromethoxy radical is preferred.“Predominantly” in this connection means that more than half of thehydrogen atoms of the 1-4C-alkoxy groups are replaced by fluorine atoms.

1-4C-Alkoxy-2-4C-alkyl stands for one of the abovementioned 2-4C-alkylradicals which is substituted by one of the abovementioned 1-4C-alkoxyradicals. Examples which may be mentioned are the 2-(methoxy)ethyl(—CH₂—CH₂—O—CH₃), the 3-(methoxy)propyl (—CH₂—CH₂—CH₂—O—CH₃), the2-(ethoxy)ethyl (—CH₂—CH₂—O—CH₂—CH₃) and the 2-(isopropoxy)ethyl(—CH₂—CH₂—O—CH—(CH₃)₂) radical.

Hydroxy-2-4C-alkyl stands for one of the abovementioned 2-4C-alkylradicals which is substituted by an hydroxyl radical. Examples which maybe mentioned are the 2-hydroxyethyl and the 3-hydroxypropyl radical.

Mono- or Di-1-4C-alkylamino radicals contain in addition to the nitrogenatom, one or two of the abovementioned 1-4C-alkyl radicals. Preferredare the di-1-4C-alkylamino radicals, especially the dimethylamino, thediethylamino and the diisopropylamino radical.

Mono- or Di-1-4C-alkylamino-2-4C-alkyl stands for one of theabovementioned 2-4C-alkyl radicals which is substituted by one of theabovementioned mono- or di-1-4C-alkylamino radicals. An example whichmay be mentioned is the 2-(dimethylamino)ethyl radical.

Phenyl-1-4C-alkyl stands for one of the abovementioned 1-4C-alkylradicals, which is substituted by a phenyl radical. Examples which maybe mentioned are the phenethyl and the benzyl radical.

1-4C-Alkylcarbonyl is a carbonyl group to which one of theabovementioned 1-4C-alkyl radicals is bonded. An example is the acetyl[CH₃—C(O)—] radical.

N-oxide denotes the N-oxide on the pyridine which is substituted by—OR5.

-   Het refers in a first aspect (aspect a) to a fully saturated or    partially unsaturated mono- or fused bicyclic ring or ring system    made up of    -   a first constituent being a 3- to 7-membered monocyclic fully        saturated non-aromatic heterocyclic ring B,        -   which heterocyclic ring B comprises one to three heteroatoms            independently selected from nitrogen, oxygen and sulfur,        -   and which heterocyclic ring B is optionally substituted by            one or two oxo groups,    -   and, optionally, fused to said first constituent,    -   a second constituent being a benzene ring,    -   and which ring Het is optionally substituted by R21 on a ring        carbon atom,    -   and/or which ring Het is optionally substituted by R22 on a        further ring carbon atom,    -   and/or which ring Het is optionally substituted by an        ethylenedioxy group,    -   and/or which ring Het is optionally substituted by R23 on a ring        nitrogen atom.

Examples for Het according to aspect a may include, but are not limitedto, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, homopiperidinyl,pyrazolidinyl, imidazolidinyl, piperazinyl, homopiperazinyl, morpholinylor thiomorpholinyl,

and the oxo substituted derivatives of the aforementioned examples suchas e.g. 2-oxopyrrolidinyl, 2-oxoimidazolidinyl, 2-oxopiperidinyl,2,5-dioxopyrrolidinyl, 2,5-dioxoimidazolidinyl, 2,6-dioxopiperidinyl,2-oxopiperazinyl, or 5-oxo-1,4-diazepanyl, as well as thiomorpholineS-oxide or thiomorpholine S,S-dioxide,

and the benzo-fused derivatives of the aforementioned examples such ase.g. indolinyl, isoindolinyl, 1,2,3,4-tetrahydroquinolinyl or1,2,3,4-tetrahydroisoquinolinyl.

As used herein, the term “oxo” forms a carbonyl moiety when attached ata carbon atom, a sulfoxide moiety when attached to a sulfur atom and asulfonyl moiety when two of said terms are attached to a sulfur atom.

Het refers in a second aspect (aspect b), which is an embodiment ofaspect a, to a 3- to 10-membered saturated or partially saturatedheterocyclic ring radical comprising totally 1 to 3 heteroatoms selectedfrom a group consisting of oxygen, sulfur and nitrogen, and optionallysubstituted by R21 on a ring carbon atom and/or by R22 on a further ringcarbon atom and/or by R23 on a ring nitrogen atom.

Exemplary Het radicals according to aspect b may be optionallysubstituted by R21 and/or R22 and/or R23 and may include, without beingrestricted thereto, azetidin-1-yl, pyrrolidin-1-yl, piperazin-1-yl,imidazolidin-1-yl, thiomorpholin-4-yl, homopiperidin-1-yl,homopiperazin-1-yl, indolin-1-yl, isoindolin-1-yl,1,2,3,4-tetrahydroquinolin-1-yl, piperidin-1-yl, morpholin-4-yl,1,2,3,4-tetrahydroisoquinolin-2-yl, 1,4-diazepan-5-one-1-yl,piperazin-3-one-1-yl, or 1,4-dioxa-8-azaspiro[4.5]decan-8-yl.

In this context, as more detailed examples for Het according to aspect bcan be mentioned, without being restricted thereto,

piperidin-1-yl, morpholin-4-yl, azetidin-1-yl, pyrrolidin-1-yl, or1,4-dioxa-8-azaspiro[4.5]decan-8-yl. Additionally, as more detailedexamples for Het according to aspect b can be also mentioned, withoutbeing restricted thereto,

piperidin-1-yl substituted by R21,preferably in which

-   R21 is 1-4C-alkyl or phenylcarbonyl,-   such as, for example, 4-methyl-piperidin-1-yl, or    4-benzoyl-piperidin-1-yl; 1,2,3,4-tetrahydroisoquinolin-2-yl    substituted by R21 and/or R22, preferably in which-   R21 is 1-4C-alkoxy, and-   R22 is 1-4C-alkoxy,    such as, for example,    6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl, or    6,7-diethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl;    piperazin-1-yl substituted by R23 on 4-N,    suitably in which-   R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,    1-4C-alkoxy-2-4C-alkyl, mono- or di-1-4C-alkylamino-2-4C-alkyl,    phenyl, pyrimidyl, pyridyl, formyl, 3-7C-cycloalkyl,    3-7C-cycloalkylmethyl, or R231- and/or R232-substituted phenyl, in    which-   R231 is halogen, cyano or 1-4C-alkyl, and-   R232 is halogen or 1-4C-alkyl,    and preferably in which-   R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/or R232-substituted    phenyl, in which-   R231 is halogen, cyano or 1-4C-alkyl, and-   R232 is halogen or 1-4C-alkyl,    such as, for example, 4-N-methyl-piperazin-1-yl,    4-N-ethyl-piperazin-1-yl, 4-N-benzyl-piperazin-1-yl,    4-N-(2-phenethyl)-piperazin-1-yl,    4-N-(2-methoxyethyl)-piperazin-1-yl, 4-N-acetyl-piperazin-1-yl,    4-N-phenyl-piperazin-1-yl, 4-N-(3,5-dichlorophenyl)-piperazin-1-yl,    4-N-(4-cyanophenyl)-piperazin-1-yl,    4-N-(4-methylphenyl)-piperazin-1-yl,    4-N-(2-methylphenyl)-piperazin-1-yl,    4-N-(2,4-dimethylphenyl)-piperazin-1-yl, or    4-N-(2,6-dimethylphenyl)-piperazin-1-yl;    1,4-diazepan-5-one-1-yl substituted by R23 on 4-N,    preferably in which-   R23 is 1-4C-alkyl or phenyl-1-4C-alkyl,    such as, for example, 4-N-methyl-1,4-diazepan-5-one-1-yl,    4-N-ethyl-1,4-diazepan-5-one-1-yl, or    4-N-benzyl-1,4-diazepan-5-one-1-yl; or    homopiperazin-1-yl substituted by R23 on 4-N,    preferably in which-   R23 is 1-4C-alkyl,    such as, for example, 4-N-methyl-homopiperazin-1-yl.

Suitable salts for compounds of the formula I—depending onsubstitution—are all acid addition salts or all salts with bases.Particular mention may be made of the pharmacologically tolerableinorganic and organic acids and bases customarily used in pharmacy.Those suitable are, on the one hand, water-insoluble and, particularly,water-soluble acid addition salts with acids such as, for example,hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid,sulphuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid,2-(4-hydroxybenzoyl)benzoic acid, butyric acid, sulphosalicylic acid,maleic acid, lauric acid, malic acid, fumaric acid, succinic acid,oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulphonicacid, methanesulphonic acid or 3-hydroxy-2-naphthoic acid, the acidsbeing employed in salt preparation—depending on whether a mono- orpolybasic acid is concerned and depending on which salt is desired—in anequimolar quantitative ratio or one differing therefrom.

On the other hand, salts with bases are—depending on substitution—alsosuitable. As examples of salts with bases are mentioned the lithium,sodium, potassium, calcium, aluminium, magnesium, titanium, ammonium,meglumine or guanidinium salts, here, too, the bases being employed insalt preparation in an equimolar quantitative ratio or one differingtherefrom.

Pharmacologically intolerable salts, which can be obtained, for example,as process products during the preparation of the compounds according tothe invention on an industrial scale, are converted intopharmacologically tolerable salts by processes known to the personskilled in the art.

According to expert's knowledge the compounds of the invention as wellas their salts may contain, e.g. when isolated in crystalline form,varying amounts of solvents. Included within the scope of the inventionare therefore all solvates and in particular all hydrates of thecompounds of formula I as well as all solvates and in particular allhydrates of the salts of the compounds of formula I.

A person skilled in the art knows on the base of his/her expertknowledge that the compounds according to this invention can exist, withregard to the fused imidazo ring, in different tautomeric forms such ase.g. in the 1-H form or, preferably, in the 3-H form, which is shown informula I. The invention includes all conceivable tautomers in pure formas well as in any mixing ratio. Particularly the present inventionincludes the pure 1-H- and, preferably, 3-H-tautomers as well as anymixtures thereof.

Compounds according to embodiment a of this invention worthy to bementioned are compounds of formula I,

in which

-   R1 is hydrogen or 1-4C-alkyl,-   R2 is hydrogen or 1-4C-alkyl, and-   R3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantly    fluorine-substituted 1-4C-alkoxy;    or in which-   R1 is 3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/or    R12-substituted phenyl, in which-   R11 is 1-4C-alkyl, halogen, 1-4C-alkoxy, or di-1-4C-alkylamino,-   R12 is 1-4C-alkyl or halogen,-   R2 is hydrogen, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or    1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkyl, trifluoromethyl, or completely    or predominantly fluorine-substituted 1-4C-alkoxy;    or in which-   R1 and R2 together and with inclusion of the nitrogen atom, to which    they are bonded, form a heterocyclic ring Het, in which    Het is a fully saturated or partially unsaturated mono- or fused    bicyclic ring or ring system made up of    -   a first constituent being a 3- to 7-membered monocyclic fully        saturated non-aromatic heterocyclic ring B,        -   which heterocyclic ring B is piperazine, morpholine,            thiomorpholine, homopiperazine, piperidine, pyrrolidine or            azetidine,        -   and which heterocyclic ring B is optionally substituted by            one or two oxo groups,    -   and, optionally, fused to said first constituent,    -   a second constituent being a benzene ring,    -   and which ring Het is optionally substituted by R21 on a ring        carbon atom,    -   and/or which ring Het is optionally substituted by R22 on a        further ring carbon atom,    -   and/or which ring Het is optionally substituted by an        ethylenedioxy group,    -   and/or which ring Het is optionally substituted by R23 on a ring        nitrogen atom,    -   in which-   R21 is 1-4C-alkyl, 1-4C-alkoxy or phenylcarbonyl,-   R22 is 1-4C-alkyl or 1-4C-alkoxy,-   R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/or R232-substituted    phenyl, in which-   R231 is halogen, cyano or 1-4C-alkyl,-   R232 is halogen or 1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkyl, trifluoromethyl, or completely    or predominantly fluorine-substituted 1-4C-alkoxy;    and in which-   R4 is hydrogen, or 1-4C-alkyl,-   R5 is methyl,-   A is ethylene;    the salts, N-oxides and the salts of the N-oxides of these    compounds.

Compounds according to embodiment b of this invention worthy to bementioned are compounds of formula I, in which

-   R1 is hydrogen or 1-4C-alkyl,-   R2 is hydrogen or 1-4C-alkyl, and-   R3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantly    fluorine-substituted 1-4C-alkoxy;    or-   R1 is 3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,    phenyl, pyridyl, or R11- and/or R12-substituted phenyl, in which    either-   R11 is 1-4C-alkyl, 1-4C-alkoxy, or mono- or di-1-4C-alkylamino, and-   R12 is halogen,    or-   R11 is halogen, 1-4C-alkoxy, or mono- or di-1-4C-alkylamino, and-   R12 is 1-4C-alkyl,-   R2 is hydrogen, hydroxy-2-4C-alkyl or 1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl,    or completely or predominantly fluorine-substituted 1-4C-alkoxy;    or-   R1 and R2 together and with inclusion of the nitrogen atom, to which    they are bonded, form a heterocyclic ring Het, in which-   Het is optionally substituted by R21 on a ring carbon atom and/or by    R22 on a further ring carbon atom and/or by R23 on a ring nitrogen    atom and is azetidin-1-yl, pyrrolidin-1-yl, piperazin-1-yl,    thiomorpholin-4-yl, homopiperidin-1-yl, homopiperazin-1-yl,    indolin-1-yl, isoindolin-1-yl, 1,2,3,4-tetrahydroquinolin-2-yl,    piperidin-1-yl, morpholin-4-yl, 1,2,3,4-tetrahydroisoquinolin-1-yl,    1,4-diazepan-5-one-1-yl, or 1,4-dioxa-8-azaspiro[4.5]decan-8-yl, in    which-   R21 is 1-4C-alkyl, 1-4C-alkoxy or phenylcarbonyl,-   R22 is 1-4C-alkoxy,-   R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/or R232-substituted    phenyl, in which-   R231 is halogen, cyano or 1-4C-alkyl,-   R232 is halogen or 1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl,    or completely or predominantly fluorine-substituted 1-4C-alkoxy;-   R4 is hydrogen,-   R5 is methyl,-   A is ethylene;    the salts, N-oxides and the salts of the N-oxides of these    compounds.

Compounds according to embodiment a of this invention more worthy to bementioned are compounds of formula I,

in which

-   R1 is hydrogen or 1-4C-alkyl,-   R2 is hydrogen or 1-4C-alkyl, and-   R3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantly    fluorine-substituted 1-4C-alkoxy;    or in which-   R1 is 3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/or    R12-substituted phenyl, in which-   R11 is 1-4C-alkyl, halogen, 1-4C-alkoxy, or di-1-4C-alkylamino,-   R12 is 1-4C-alkyl or halogen,-   R2 is hydrogen, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or    1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkyl, trifluoromethyl, or completely    or predominantly fluorine-substituted 1-4C-alkoxy;    or in which-   R1 and R2 together and with inclusion of the nitrogen atom, to which    they are bonded, form a heterocyclic ring Het, in which-   Het is piperidinyl, pyrrolidinyl or azetidinyl, or    -   morpholinyl, thiomorpholinyl, S-oxo-thiomorpholinyl or        S,S-dioxo-thiomorpholinyl, or 1,2,3,4-tetrahydroisoquinolinyl or        di-(1-4C-alkoxy)-1,2,3,4-tetrahydroisoquinolinyl, or piperidinyl        substituted by either ethylenedioxy or R21, or    -   4N—(R23)-piperazinyl or 4N—(R23)-homopiperazinyl, or        4N—(H)-1,4-diazepan-5-one-1-yl or        4N—(R23)-1,4-diazepan-5-one-1-yl,    -   in which-   R21 is 1-4C-alkyl, or phenylcarbonyl,-   R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/or R232-substituted    phenyl, in which-   R231 is halogen, cyano or 1-4C-alkyl,-   R232 is halogen or 1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkyl, trifluoromethyl, or completely    or predominantly fluorine-substituted 1-4C-alkoxy;    and in which-   R4 is hydrogen, or 1-4C-alkyl,-   R5 is methyl,-   A is ethylene;    the salts, N-oxides and the salts of the N-oxides of these    compounds.

Compounds according to embodiment b of this invention more worthy to bementioned are compounds of formula I, in which

-   R1 is hydrogen or 1-4C-alkyl,-   R2 is hydrogen or 1-4C-alkyl, and-   R3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantly    fluorine-substituted 1-4C-alkoxy;    or-   R1 is 3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,    phenyl, pyridyl, or R11- and/or R12-substituted phenyl, in which    either-   R11 is 1-4C-alkyl, 1-4C-alkoxy, or mono- or di-1-4C-alkylamino, and-   R12 is halogen,

Or

-   R11 is halogen, 1-4C-alkoxy, or mono- or di-1-4C-alkylamino, and-   R12 is 1-4C-alkyl,-   R2 is hydrogen, hydroxy-2-4C-alkyl or 1-4C-alkyl, and-   R3 is halogen, 1-4C-alkyl, trifluoromethyl, completely or    predominantly fluorine-substituted 1-4C-alkoxy, or, particularly,    hydrogen;    or-   R1 and R2 together and with inclusion of the nitrogen atom, to which    they are bonded, form a heterocyclic ring Het, in which-   Het is piperidin-1-yl, or piperidin-1-yl substituted by R21, in    which-   R21 is 1-4C-alkyl or phenylcarbonyl,    or-   Het is 1,2,3,4-tetrahydroisoquinolin-2-yl substituted by R21 and    R22, in which-   R21 is 1-4C-alkoxy,-   R22 is 1-4C-alkoxy,    or-   Het is piperazin-1-yl substituted by R23 on 4-N, in which-   R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/or R232-substituted    phenyl, in which-   R231 is halogen, cyano or 1-4C-alkyl,-   R232 is halogen or 1-4C-alkyl,    or-   Het is 1,4-diazepan-5-one-1-yl, or 1,4-diazepan-5-one-1-yl    substituted by R23 on 4-N, in which-   R23 is 1-4C-alkyl or phenyl-1-4C-alkyl,    or-   Het is homopiperazin-1-yl substituted by R23 on 4-N, in which-   R23 is 1-4C-alkyl,    or-   Het is morpholin-4-yl, azetidin-1-yl, pyrrolidin-1-yl, or    1,4-dioxa-8-azaspiro[4.5]decan-8-yl, and-   R3 is hydrogen, halogen, 1-4C-alkyl, trifluoromethyl, or completely    or predominantly fluorine-substituted 1-4C-alkoxy;-   R4 is hydrogen,-   R5 is methyl,-   A is ethylene;    the salts, N-oxides and the salts of the N-oxides of these    compounds.

Compounds according to embodiment a of this invention in particularworthy to be mentioned are compounds of formula I,

in which

-   R1 is hydrogen or 1-4C-alkyl,-   R2 is hydrogen or 1-4C-alkyl, and-   R3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantly    fluorine-substituted 1-4C-alkoxy;    or in which-   R1 is 3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/or    R12-substituted phenyl, in which    either-   R11 is 1-4C-alkyl, 1-4C-alkoxy, or di-1-4C-alkylamino, and-   R12 is halogen,    or-   R11 is halogen, 1-4C-alkoxy, or di-1-4C-alkylamino, and-   R12 is 1-4C-alkyl,-   R2 is hydrogen, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or    1-4C-alkyl, and-   R3 is hydrogen;    or in which-   R1 and R2 together and with inclusion of the nitrogen atom, to which    they are bonded, form a heterocyclic ring Het, in which-   Het is piperidinyl, pyrrolidinyl or azetidinyl, or    -   morpholinyl, thiomorpholinyl, S-oxo-thiomorpholinyl or        S,S-dioxo-thiomorpholinyl, or 1,2,3,4-tetrahydroisoquinolinyl or        di-(1-4C-alkoxy)-1,2,3,4-tetrahydroisoquinolinyl, or piperidinyl        substituted by either ethylenedioxy or R21, or    -   4N—(R23)-piperazinyl or 4N—(1-4C-alkyl)-homopiperazinyl, or        4N—(H)-1,4-diazepan-5-one-1-yl,        4N—(phenyl-1-4C-alkyl)-1,4-diazepan-5-one-1-yl or        4N-(1-4C-alkyl)-1,4-diazepan-5-one-1-yl,    -   in which-   R21 is 1-4C-alkyl, or phenylcarbonyl,-   R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,    1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/or R232-substituted    phenyl, in which-   R231 is halogen, cyano or 1-4C-alkyl,-   R232 is halogen or 1-4C-alkyl, and-   R3 is hydrogen, halogen, 1-4C-alkyl, trifluoromethyl, or completely    or predominantly fluorine-substituted 1-4C-alkoxy;    and in which-   R4 is hydrogen, or 1-4C-alkyl,-   R5 is methyl,-   A is ethylene;    the salts, N-oxides and the salts of the N-oxides of these    compounds.

Compounds according to embodiment b of this invention in particularworthy to be mentioned are compounds of formula I, in which

-   R1 is methyl,-   R2 is methyl, and-   R3 is methyl, trifluoromethyl or trifluoromethoxy;    or-   R1 is cyclohexyl, benzyl, 2-hydroxyethyl, phenyl, pyridyl, or R11-    and/or R12-substituted phenyl, in which    either-   R11 is methyl, methoxy or dimethylamino, and-   R12 is chlorine or fluorine,    or-   R11 is chlorine, fluorine, methoxy or dimethylamino, and-   R12 is methyl,-   R2 is hydrogen or methyl,    or R1 and R2 are both 2-hydroxyethyl, and-   R3 is hydrogen;    or-   R1 and R2 together and with inclusion of the nitrogen atom, to which    they are bonded, form a heterocyclic ring Het, in which-   Het is piperidin-1-yl, or piperidin-1-yl substituted by R21, in    which-   R21 is methyl or phenylcarbonyl,    or-   Het is 1,2,3,4-tetrahydroisoquinolin-2-yl substituted by R21 and    R22, in which-   R21 is methoxy,-   R22 is methoxy,    or-   Het is piperazin-1-yl substituted by R23 on 4-N, in which-   R23 is methyl, ethyl, benzyl, phenethyl, acetyl, 2-methoxyethyl,    phenyl, or R231- and/or R232-substituted phenyl, in which-   R231 is chlorine, cyano or methyl,-   R232 is chlorine or methyl,    or-   Het is 1,4-diazepan-5-one-1-yl, or 1,4-diazepan-5-one-1-yl    substituted by R23 on 4-N, in which-   R23 is methyl, ethyl or benzyl,    or-   Het is homopiperazin-1-yl substituted by R23 on 4-N, in which-   R23 is methyl,

Or

-   Het is morpholin-4-yl, azetidin-1-yl, pyrrolidin-1-yl, or    1,4-dioxa-8-azaspiro[4,5]decan-8-yl, and-   R3 is hydrogen, fluorine, chlorine, methyl, trifluoromethyl or    trifluoromethoxy;-   R4 is hydrogen,-   R5 is methyl,-   A is ethylene;    the salts, N-oxides and the salts of the N-oxides of these    compounds.

Compounds according to embodiment a of this invention in more particularworthy to be mentioned are compounds of formula I,

in which

-   R1 is methyl,-   R2 is methyl, and-   R3 is methyl, trifluoromethyl, or trifluoromethoxy;    or in which-   R1 is cyclohexyl, cyclobutyl, cyclopropyl, benzyl, 2-hydroxy-ethyl,    2-methoxy-ethyl, phenyl, pyridyl, or R11- and/or R12-substituted    phenyl, in which    either-   R11 is methyl, methoxy, or dimethylamino, and-   R12 is fluorine,    or-   R11 is fluorine, chlorine, methoxy, or dimethylamino, and-   R12 is methyl,-   R2 is hydrogen, 2-hydroxy-ethyl, 2-methoxy-ethyl, or methyl, and-   R3 is hydrogen;    or in which-   R1 and R2 together and with inclusion of the nitrogen atom, to which    they are bonded, form a heterocyclic ring Het, in which-   Het is piperidinyl, pyrrolidinyl or azetidinyl, or    -   morpholinyl, thiomorpholinyl, S-oxo-thiomorpholinyl or        S,S-dioxo-thiomorpholinyl, or 1,2,3,4-tetrahydroisoquinolinyl,        di-methoxy-1,2,3,4-tetrahydroisoquinolinyl, or        di-ethoxy-1,2,3,4-tetrahydroisoquinolinyl, or    -   4,4-ethylenedioxy-piperidinyl or 4-(R21)-piperidinyl, or    -   4N—(R23)-piperazinyl or 4N-methyl-homopiperazinyl, or        4N—(H)-1,4-diazepan-5-one-1-yl,        4N-benzyl-1,4-diazepan-5-one-1-yl,        4N-methyl-1,4-diazepan-5-one-1-yl, or        4N-ethyl-1,4-diazepan-5-one-1-yl,    -   in which-   R21 is methyl, or phenylcarbonyl,-   R23 is methyl, ethyl, benzyl, phenethyl, acetyl, 2-methoxy-ethyl,    phenyl, or R231- and/or R232-substituted phenyl, in which    either-   R231 is chlorine, cyano or methyl, and-   R232 is chlorine,    or-   R231 is chlorine, cyano or methyl, and-   R232 is methyl, and-   R3 is hydrogen, fluorine, chlorine, methyl, trifluoromethyl, or    trifluoromethoxy; and in which-   R4 is hydrogen, or methyl,-   R5 is methyl,-   A is ethylene;    the salts, N-oxides and the salts of the N-oxides of these    compounds.

A special embodiment of the compounds of the present invention includethose compounds of formula I in which R5 is methyl.

Another special embodiment of the compounds of the present inventioninclude those compounds of formula I in which A is ethylene.

Another special embodiment of the compounds of the present inventioninclude those compounds of formula I in which R5 is methyl and A isethylene.

Another special embodiment of the compounds of the present inventioninclude those compounds of formula I in which R4 is hydrogen.

Another special embodiment of the compounds of the present inventioninclude those compounds of formula I in which R4 is methyl.

Another special embodiment of the compounds of the present inventioninclude those compounds of formula I in which R4 is hydrogen, R5 ismethyl and A is ethylene.

Another special embodiment of the compounds of the present inventioninclude those compounds of formula I in which R4 is methyl, R5 is methyland A is ethylene.

Another special embodiment of the compounds of the present inventioninclude those compounds of formula I in which the aminosulphonylphenylmoiety is bonded to the 6-position of the imidazopyridine ring system.

The substituent R3 and the aminosulphonyl radical of compounds accordingto this invention can be attached in the ortho, meta or para positionwith respect to the binding position in which the phenyl ring is bondedto the imidazopyridine ring system, whereby a special embodiment of thecompounds of the present invention include those compounds of formula Iin which the aminosulphonyl radical is attached in the meta or,particularly, para position.

In this context, another embodiment of the compounds of the presentinvention include those compounds of formula I in which R3 is attachedin the ortho or meta position and the aminosulphonyl radical is attachedin the para position with respect to the binding position in which thephenyl ring is bonded to the imidazopyridine ring system.

The substituents R11 and R12 of compounds according to this inventioncan be attached in the ortho, meta or para position with respect to thebinding position in which the phenyl ring is bonded to the nitrogenatom.

The substituents R231 and R232 of compounds according to this inventioncan be attached in the ortho, meta or para position with respect to thebinding position in which the phenyl ring is bonded to the ring nitrogenatom.

Compounds of formula I can be obtained as described below and shown inthe following reaction schemes, or as specified by way of example in thefollowing examples or similarly or analogously thereto.

Thus, as shown in reaction scheme 1 below, a compound of formula II, inwhich R4, R5 and A have the meanings given above and X is a suitableleaving group, preferably bromine or, particularly, iodine, is reactedwith boronic acids or, particularly, boronic acid esters (e.g. pinacolesters) of formula III, in which R1, R2 and R3 have the meanings givenabove and Y is a boronic acid group or, particularly, a boronic acidester group, suitably a cyclic boronic acid ester group such as, forexample, the boronic acid pinacol ester group, under conditionsappropriate for a Suzuki reaction to occur to give compounds of formulaI, in which R1, R2, R3, R4, R5 and A have the meanings mentioned above.

Suitably, the Suzuki reaction is carried out as it is known to theperson of ordinary skill in the art and/or in a manner as it isdescribed below and specified by way of example in the followingexamples or analogously or similarly thereto.

In more detail, the Suzuki reaction mentioned can be carried out inorganic solvents alone, for example in toluene, benzene,dimethylformamide or in ethereal (e.g. dimethoxyethane or, inparticular, dioxane) or alcohol solvents or in a mixture thereof, orpreferably in a mixture comprising an organic solvent (in particulardioxane) and water, with organic (e.g. triethylamine) or preferablyinorganic base (e.g. potassium hydroxide, thallium hydroxide, sodiumbicarbonate, cesium carbonate, cesium fluoride or, in particular,potassium carbonate) in the presence of a transition metal catalyst, forexample, a nickel or, in particular, palladium catalyst (e.g. Pd(OAc)₂,PdCl₂(PPh₃)₂ or, in particular, Pd(PPh₃)₄), and, optionally, lithiumchloride. The reaction is carried out at a temperature in the range from20° to 160° C., usually 60° to 130° C. for 10 minutes to 5 days, usually30 minutes to 24 hours. Advantageously, the solvents used are degassedand the reaction is carried out under protective gas.

The Suzuki reaction is for example described in Tetrahedron Lett. 1998,39, 4467, J. Org. Chem. 1999, 64, 1372 or Heterocycles 1992, 34, 1395. Ageneral review of Suzuki cross-couplings between boronic acids and arylhalides can be found in Miyaura, N; Suzuki, A. Chem. Rev. 1995, 95,2457.

Boronic acids or boronic acid esters (e.g. pinacol esters) of formulaIII, in which R1, R2, R3 and Y have the meanings given above, are knownor can be obtained in an art-known manner or analogously or similarly toknown compounds. Boronic acid esters (e.g. pinacol esters) of formulaIII can be prepared, for example, as described in the following examplesstarting from phenyl triflates or, particularly, phenyl halides,preferably the bromides or iodides, using e.g. bis-(pinacolato)-diboronin the presence of a transition metal, preferably palladium, catalyst.Optionally the boronic acid esters obtained can be isolated or,preferably, they are generated in situ and used in the subsequent Suzukireaction without isolation.

Compounds of formula II, in which R4, R5, X and A have the meaningsgiven above, are obtained as exemplarily described in the followingexamples or shown in the following reaction scheme 2 or similarly oranalogously thereto.

In the following reaction scheme 2 the synthesis of compounds of formulaII, in which R4, R5 and X have the meanings given above and A isethylene, is exemplarily described.

The carbon chain in 2-position of the compounds of formula VII islengthened, for example, by a condensation (with a malonic acidderivative) and a subsequent hydrogenation reaction. Alternatively, thecarbon chain can be lengthened using a Wittig reaction followed by ahydrogenation reaction.

The methyl 3-(4-(1-4C)-alkoxypyridin-2-yl)propionate (compound offormula V) or the corresponding acid (compound of formula IV), which canbe obtained in an art-known manner, are converted with a2,3-diaminopyridine derivative (compound of formula III) to give thedesired compounds of formula II.

The synthesis of 4-methoxy-pyridin-2-carbaldehyde (compound of formulaVII) is described for example in Ashimori et al, Chem Pharm Bull 38,2446-2458 (1990).

Compounds of formula VII can be also prepared starting from commerciallyavailable 4-nitro-2-picoline-N-oxide by exchange of the nitro group byan 1-4C-alkoxy group. The resulting 4-(1-4C)-alkoxy-2-picoline-N-oxideis then via a rearrangement and an oxidation step converted to4-(1-4C)-alkoxy-pyridin-2-carbaldehyd (compound of formula VII).

The synthesis of 3-(4-methoxypyridin-2-yl)propionic acid (compound offormula IV) is described in the paragraph Starting Materials.

Compounds of formula III, in which R4 and X have the meanings indicatedabove, are known or can be prepared in a known manner or analogously orsimilarly to the preparation of art-known compounds.

Optionally, compounds of formula I can be converted into their salts,or, optionally, salts of the compounds of formula I can be convertedinto the free compounds. Corresponding processes are known to the personskilled in the art.

The compounds of formula I according to this invention can be converted,optionally, into their N-oxides, for example with the aid of hydrogenperoxide in methanol or with the aid of m-chloroperoxybenzoic acid indichloromethane. The person skilled in the art is familiar on the basisof his/her expert knowledge with the reaction conditions which arespecifically necessary for carrying out the N-oxidation.

It is known to the person skilled in the art that if there are a numberof reactive centers on a starting or intermediate compound it may benecessary to block one or more reactive centers temporarily byprotective groups in order to allow a reaction to proceed specificallyat the desired reaction center. A detailed description for the use of alarge number of proven protective groups is found, for example, in T. W.Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, 1999,3^(rd) Ed, or in P. Kocienski, Protecting Groups, Thieme MedicalPublishers, 2000.

The substances according to the invention are isolated and purified in amanner known per se, e.g. by distilling off the solvent in vacuo andrecrystallizing the residue obtained from a suitable solvent orsubjecting it to one of the customary purification methods, such ascolumn chromatography on a suitable support material.

Salts are obtained by dissolving the free compound in a suitable solvent(for example a ketone like acetone, methylethylketone, ormethylisobutylketone, an ether, like diethyl ether, tetrahydrofuran ordioxane, a chlorinated hydrocarbon, such as methylene chloride orchloroform, or a low molecular weight aliphatic alcohol, such asethanol, isopropanol) which contains the desired acid, or to which thedesired acid is then added. The salts are obtained by filtering,reprecipitating, precipitating with a non-solvent for the addition saltor by evaporating the solvent. Salts obtained can be converted bybasification into the free compounds which, in turn, can be convertedinto salts. In this manner, pharmacologically non-tolerable salts can beconverted into pharmacologically tolerable salts.

Suitably, the conversions mentioned in this invention can be carried outanalogously or similarly to methods which are familiar per se to theperson skilled in the art, for example, in the manner which is describedby way of example in the following examples.

The person skilled in the art knows on the basis of his/her knowledgeand on the basis of those synthesis routes, which are shown anddescribed within the description of this invention, how to find otherpossible synthesis routes for compounds according to this invention. Allthese other possible synthesis routes are also part of this invention.

Having described the invention in detail, the scope of the presentinvention is not limited only to those described characteristics orembodiments. As will be apparent to persons skilled in the art,modifications, analogies, variations, derivations, homologisations andadaptations to the described invention can be made on the base ofart-known knowledge and/or, particularly, on the base of the disclosure(e.g. the explicite, implicite or inherent disclosure) of the presentinvention without departing from the spirit and scope of this inventionas defined by the scope of the appended claims.

The following examples illustrate the invention in greater detail,without restricting it. As well, further compounds according to thepresent invention, of which the preparation is explicitly not described,can be prepared in an analogous way or in a way which is known by aperson skilled in the art using customary preparation methods andprocess techniques.

The compounds, which are mentioned in the examples as well as theirsalts are a preferred subject of the invention.

In the examples, m.p. stands for melting point, h for hours, d for days,min for minutes, TLC for thin layer chromatography, Rf for retentionfactor, MS for mass spectrum, M for molecular ion, other abbreviationshave their meanings customary per se for the skilled person.

EXAMPLES Final Products 1.2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-methylpiperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine

A mixture of 1.12 g of 1-(4-bromo-benzene-sulfonyl)-4-methyl-piperazine,0.978 g of bis-(pinacolato)-diboron, 0.06 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.077 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 1.03 g of potassium acetate in 40 ml of degassed dioxaneare heated to 90° C. under N₂ for 8 hours. To the resulting mixture 15ml of degassed dioxane, 0.931 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.283 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.678 g ofpotassium carbonate and 0.208 g of lithium chloride in 15 ml of degassedwater are added under N₂. The mixture is heated to reflux under N₂ for16 hours and, after cooling, addition of water and adjusting the pH to7, it is extracted three times with dichloromethane. The combinedorganic phases are dried over sodium sulfate, concentrated and theresidue is chromatographed on a silica gel column(dichloromethane/methanol 15-10:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate gives 0.545 g of the title compound as a solid of m.p.193-195° C. The mass spectrum shows the molecular peak MH⁺ at 493.4 Da.

2.2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-benzylpiperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine

A mixture of 0.593 g of1-(4-bromo-benzene-sulfonyl)-4-benzyl-piperazine, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 8 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 16 hours. To theresulting mixture 4 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 4 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 110° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withethylacetate. The combined organic phases are dried over sodium sulfate,concentrated and the residue is chromatographed on a silica gel column(dichloromethane/methanol 22-20:1+1% NEt₃). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate gives 0.128 g of the title compound as a brownishsolid of m.p. 160-162° C. The mass spectrum shows the molecular peak MH⁺at 569.4 Da.

3.2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-phenylpiperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine

A mixture of 0.572 g of1-(4-bromo-benzene-sulfonyl)-4-phenyl-piperazine, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 8 ml degassed dioxane areheated to 90° C. in a sealed tube under N₂ for 7 hours. To the resultingmixture 4 ml of degassed dioxane, 0.399 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.121 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.29 g ofpotassium carbonate and 0.089 g of lithium chloride in 4 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withethylacetate. The combined organic phases are dried over sodium sulfate,concentrated and the residue is chromatographed on a silica gel column(dichloromethane/methanol 28-26:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom acetonitril/methanol (3:1) gives 0.27 g of the title compound as abrownish solid of m.p. 218-220° C. The mass spectrum shows the molecularpeak MH⁺ at 555.4 Da.

4.2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-{4-[4-(4-cyanophenyl)-piperazin-1-yl-sulfonyl]-phenyl}-3H-imidazo-[4,5-b]pyridine

A mixture of 0.406 g of1-(4-bromo-benzene-sulfonyl)-4-(4-cyanophenyl)-piperazine, 0.28 g ofbis-(pinacolato)-diboron, 0.017 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.022 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.294 g of potassium acetate in 6 ml of degassed dioxaneare heated to 85° C. in a sealed tube under N₂ for 18 hours. To theresulting mixture 4 ml of degassed dioxane, 0.228 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.069 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.165 g ofpotassium carbonate and 0.051 g of lithium chloride in 4 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 110° under N₂ for 5 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withethylacetate. The combined organic phases are dried over sodium sulfate,concentrated and the residue is crystallized from ethylacetate.Recrystallization from ethylacetate and then from acetonitril gives0.295 g of the title compound as a brownish solid of m.p. 217-219° C.The mass spectrum shows the molecular peak MH⁺ at 580.5 Da.

5.2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-p-tolyl-piperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine

A mixture of 0.395 g of1-(4-bromo-benzene-sulfonyl)-4-(p-tolyl)-piperazine, 0.28 g ofbis-(pinacolato)-diboron, 0.017 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.022 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.294 g of potassium acetate in 6 ml of degassed dioxaneare heated to 85° C. in a sealed tube under N₂ for 16 hours. To theresulting mixture 4 ml of degassed dioxane, 0.228 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.069 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.165 g ofpotassium carbonate and 0.051 g of lithium chloride in 4 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 7.5 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withethylacetate. The combined organic phases are dried over sodium sulfate,concentrated and the residue is chromatographed on a silica gel column(dichloromethane/methanol 25-20:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate/diethylether gives 0.128 g of the title compound as abrownish solid of m.p. 150-154° C. The mass spectrum shows the molecularpeak MH⁺ at 569.5 Da.

6.6-{4-[4-(2,4-Dimethylphenyl)-piperazin-1-yl-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine

A mixture of 0.614 g of1-(4-bromo-benzene-sulfonyl)-4-(2,4-dimethylphenyl)-piperazine, 0.42 gof bis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 8 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 7 hours. To theresulting mixture 10 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 10 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 23 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withethylacetate. The combined organic phases are dried over sodium sulfate,concentrated and the residue is chromatographed on a silica gel column(dichloromethane/methanol 25-20:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate gives 0.27 g of the title compound as a solid of m.p.208-209° C. The mass spectrum shows the molecular peak MH⁺ at 583.5 Da.

7.6-{4-[4-(3,5-Dichlorphenyl)-piperazin-1-yl-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine

A mixture of 0.675 g of1-(4-bromo-benzene-sulfonyl)-4-(3,5-dichlorphenyl)-piperazine, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 8 ml of degassed dioxaneare heated to 85° C. in a sealed tube under N₂ for 6 hours. To theresulting mixture 4 ml of degassed dioxane, 0.342 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.104 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.25 g ofpotassium carbonate and 0.076 g of lithium chloride in 4 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 110° under N₂ for 17 hours and, after cooling; addition ofwater and adjusting the pH to 7, it is extracted three times withethylacetate. The combined organic phases are dried over sodium sulfate,concentrated and the residue is chromatographed on a silica gel column(dichloromethane/methanol 28-24:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate gives 0.047 g of the title compound as a solid of m.p.220-222° C. The mass spectrum shows the molecular peak MH⁺ at 623.5 Da.

8.6-{4-[4-(2-Methoxy-ethyl)-piperazin-1-yl-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine

A mixture of 0.363 g of1-(4-bromo-benzene-sulfonyl)-4-(2-methoxy-ethyl)-piperazine, 0.28 g ofbis-(pinacolato)-diboron, 0.017 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.022 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.294 g of potassium acetate in 6 ml degassed dioxane areheated to 85° C. in a sealed tube under N₂ for 20 hours. To theresulting mixture 4 ml of degassed dioxane, 0.228 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.69 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.165 g ofpotassium carbonate and 0.051 g of lithium chloride in 4 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 7 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 25-20:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate/diethylether (9:1) gives 0.16 g of the title compoundas a solid of m.p. 206-208° C. The mass spectrum shows the molecularpeak MH⁺ at 537.4 Da.

9.6-[4-(4-Acetyl-piperazin-1-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridine

A mixture of 0.347 g of1-(4-bromo-benzene-sulfonyl)-4-acetyl-piperazine, 0.28 g ofbis-(pinacolato)-diboron, 0.017 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.022 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.294 g of potassium acetate in 6 ml of degassed dioxaneare heated to 85° C. in a sealed tube under N₂ for 20 hours. To theresulting mixture 4 ml of degassed dioxane, 0.228 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.069 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.165 g ofpotassium carbonate and 0.051 g of lithium chloride in 4 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 7 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withethylacetate. The combined organic phases are dried over sodium sulfate,concentrated and the residue is chromatographed on a silica gel column(dichloromethane/methanol 25-20:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate/diethylether (9:1) gives 0.175 g of the title compoundas a solid of m.p. 138-140° C. The mass spectrum shows the molecularpeak MH⁺ at 521.4 Da.

10.2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(morpholin-4-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine

A mixture of 0.405 g of 4-(4-bromo-benzene-sulfonyl)-morpholine, 0.42 gof bis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 8 ml degassed dioxane areheated to 90° C. in a sealed tube under N₂ for 7 hours. To the resultingmixture 4 ml of degassed dioxane, 0.399 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.121 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.29 g ofpotassium carbonate and 0.089 g of lithium chloride in 4 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withethylacetate. The combined organic phases are dried over sodium sulfate,concentrated and the residue is chromatographed on a silica gel column(dichloromethane/methanol 30-24:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate gives 0.073 g of the title compound as a solid of m.p.210-212° C. The mass spectrum shows the molecular peak MH⁺ at 480.3 Da.

11.2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-methyl-[1,4]diazepan-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine

A mixture of 0.5 g of1-(4-bromo-benzene-sulfonyl)-4-methyl-[1,4]diazepane, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 85° C. in a sealed tube under N₂ for 17 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 120° under N₂ for 7 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 22-15:1+1% NH₄OH). Concentration of thechromatographically pure fractions, crystallization of the residue fromethyl acetate and recrystallization from ethylacetate/acetonitril (4:1)gives 0.275 g of the title compound as a solid of m.p. 160-162° C. Themass spectrum shows the molecular peak MH⁺ at 507.3 Da.

12.2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-methyl-piperidin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine

A mixture of 0.477 g of1-(4-bromo-benzene-sulfonyl)-4-methyl-piperidine, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 85° C. in a sealed tube under N₂ for 6 hours. To theresulting mixture 5 ml of degassed dioxane, 0.342 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.104 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.25 g ofpotassium carbonate and 0.076 g of lithium chloride in 3 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 110° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate and concentrated. Crystallization of the residue fromethylacetate and recrystallization from acetonitril gives 0.185 g of thetitle compound as a solid of m.p. 186-188° C. The mass spectrum showsthe molecular peak MH⁺ at 492.4 Da.

13.6-[4-(4-Benzoyl-piperidin-1-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine

A mixture of 0.612 g of1-(4-bromo-benzene-sulfonyl)-4-benzoyl-piperidine, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 6 hours. To theresulting mixture 6 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 6 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 19 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 30-25:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate gives 0.21 g of the title compound as a solid of m.p.174-175° C. The mass spectrum shows the molecular peak MH⁺ at 582.3 Da.

14.6-[4-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine

A mixture of 0.543 g of8-(4-bromo-benzene-sulfonyl)-1,4-dioxa-8-azaspiro[4.5]decane, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml degassed dioxane areheated to 90° C. in a sealed tube under N₂ for 7 hours. To the resultingmixture 8 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 8 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 30-25:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate gives 0.185 g of the title compound as a solid of m.p.121-122° C. The mass spectrum shows the molecular peak MH⁺ at 536.3 Da.

15.6-[4-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine

A mixture of 0.619 g of2-(4-bromo-benzene-sulfonyl)-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline,0.42 g of bis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 9 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 7 hours. To theresulting mixture 15 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 10 ml degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 30-25:1). Concentration of thechromatographically pure fractions and crystallization of the residuefrom ethylacetate gives 0.396 g of the title compound as a solid of m.p.207-208° C. The mass spectrum shows the molecular peak MH⁺ at 586.3 Da.

16.6-[4-(1,4-Diazepan-5-one-1-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-Imidazo-[4,5-b]pyridine

A mixture of 0.50 g of 1-(4-bromo-benzene-sulfonyl)-1,4-diazepan-5-one,0.42 g of bis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenyl-phosphino)ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 17 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 7 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 20-12:1+1% NH₄OH). Concentration of thechromatographically pure fractions and crystallization of the residuefrom acetonitril gives 0.125 g of the title compound as a solid of m.p.230-232° C. The mass spectrum shows the molecular peak MH⁺ at 507.3 Da.

17.N-(2-Hydroxyethyl)-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}benzenesulfonamid

A mixture of 0.42 g of N-(2-hydroxyethyl)-4-bromobenzenesulfonamide,0.42 g of bis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 7 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 15-8:1+1% NH₄OH). Concentration of thechromatographically pure fractions and crystallisation from ethanolgives 0.20 g of the title compound as a solid of m.p. 218-220° C. Themass spectrum shows the molecular peak MH⁺ at 454.1 Da.

18.N,N-Bis-(2-hydroxyethyl)-4-{2-[2-(4-methoxypyridin-2-yl)-ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid

A mixture of 0.486 g ofN,N-bis-(2-hydroxyethyl)-4-bromobenzenesulfonamide, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 6.5 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 15-8:1+1% NH₄OH). Concentration of thechromatographically pure fractions and crystallisation from ethanolgives 0.29 g of the title compound as a solid of m.p. 127-128° C. Themass spectrum shows the molecular peak MH⁺ at 498.3 Da.

19.N-Benzyl-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid

A mixture of 0.49 g of N-benzyl-4-bromobenzenesulfonamide, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 6 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 120° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 22-15:1). Concentration of thechromatographically pure fractions and crystallisation fromethylacetate/acetonitril (1:1) gives 0.26 g of the title compound as asolid of m.p. 211-212° C. The mass spectrum shows the molecular peak MH⁺at 500.3 Da.

20.N-Cyclohexyl-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid

A mixture of 0.477 g of N-cyclohexyl-4-bromobenzenesulfonamide, 0.42 gof bis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 6 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 120° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 22-15:1). Concentration of thechromatographically pure fractions and crystallisation fromethylacetate/acetonitril (1:1) gives 0.27 g of the title compound as asolid of m.p. 199-200° C. The mass spectrum shows the molecular peak MH⁺at 492.4 Da.

21.4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N,N-dimethyl-2-trifluormethoxy-benzenesulfonamide

A mixture of 0.477 g ofN,N-dimethyl-4-bromo-2-trifluormethoxybenzenesulfonamide, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 85° C. in a sealed tube under N₂ for 19 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 120° under N₂ for 5.5 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 30-26:1). Concentration of thechromatographically pure fractions and crystallisation from ethylacetategives 0.425 g of the title compound as a solid of m.p. 145-146° C. Themass spectrum shows the molecular peak MH⁺ at 522.3 Da.

22.4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-Imidazo[4,5-b]pyridin-6-yl}-N,N-dimethyl-2-trifluormethyl-benzenesulfonamide

A mixture of 0.480 g ofN,N-dimethyl-4-bromo-2-trifluormethylbenzenesulfonamide, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 17 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 120° under N₂ for 7 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 30-25:1). Concentration of thechromatographically pure fractions and crystallisation (twice) fromethylacetate gives 0.31 g of the title compound as a solid of m.p.189-190° C. The mass spectrum shows the molecular peak MH⁺ at 506.2 Da.

23.4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N,N-dimethyl-3-methyl-benzenesulfonamide

A mixture of 0.417 g of N,N-dimethyl-4-bromo-3-methylbenzenesulfonamide,0.42 g of bis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 6 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 30-25:1). Concentration of thechromatographically pure fractions and crystallisation from ethylacetategives 0.19 g of the title compound as a solid of m.p. 179-180° C. Themass spectrum shows the molecular peak MH⁺ at 452.2 Da.

24.4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-phenyl-benzenesulfonamide

A mixture of 0.468 g of N-phenyl-4-bromo-benzenesulfonamide, 0.42 g ofbis-(pinacolato)-diboron, 0.0.25 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 6 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 120° under N₂ for 16 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 28-15:1). Concentration of thechromatographically pure fractions and crystallisation from acetonitrilgives 0.125 g of the title compound as a solid of m.p. 231-233° C. Themass spectrum shows the molecular peak MH⁺ at 507.3 Da.

25.4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-p-tolyl-benzenesulfonamide

A mixture of 0.489 g of N-p-tolyl-4-bromo-benzenesulfonamide, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 17 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 120° under N₂ for 6.5 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 25-15:1). Concentration of thechromatographically pure fractions and crystallisation fromethylacetate/acetonitril (1:1) gives 0.22 g of the title compound as asolid of m.p. 219-220° C. The mass spectrum shows the molecular peak MH⁺at 500.3 Da.

26.4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-(2-methoxyphenyl)-benzenesulfonamide

A mixture of 0.513 g of N-(2-methoxyphenyl)-4-bromo-benzenesulfonamide,0.42 g of bis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 17 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 19 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 28-20:1). Concentration of thechromatographically pure fractions and crystallisation from ethylacetategives 0.14 g of the title compound as a solid of m.p. 215-216° C. Themass spectrum shows the molecular peak MH⁺ at 516.3 Da.

27.N-(4-Dimethylamino-phenyl)-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid

A mixture of 0.400 g ofN-(4-dimethylamino-phenyl)-4-bromo-benzenesulfonamide, 0.315 g ofbis-(pinacolato)-diboron, 0.019 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.025 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.332 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 17 hours. To theresulting mixture 5 ml of degassed dioxane, 0.278 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.085 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.202 g ofpotassium carbonate and 0.062 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 17 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 25-15:1). Concentration of thechromatographically pure fractions and crystallisation from ethylacetategives 0.06 g of the title compound as a solid of m.p. 221-222° C. Themass spectrum shows the molecular peak MH⁺ at 529.2 Da.

28.N-(4-Chlorphenyl)-N-methyl-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid

A mixture of 0.541 g ofN-(4-chlorphenyl)-N-methyl-4-bromo-benzenesulfonamide, 0.42 g ofbis-(pinacolato)-diboron, 0.025 g of1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of[1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complexwith CH₂Cl₂), 0.442 g of potassium acetate in 6 ml of degassed dioxaneare heated to 90° C. in a sealed tube under N₂ for 17 hours. To theresulting mixture 5 ml of degassed dioxane, 0.371 g of2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1), 0.113 g oftetrakis(triphenylphosphine)-palladium(0) and a solution of 0.27 g ofpotassium carbonate and 0.083 g of lithium chloride in 5 ml of degassedwater are added under N₂. The tube is sealed again, the mixture isheated to 115° under N₂ for 6 hours and, after cooling, addition ofwater and adjusting the pH to 7, it is extracted three times withdichloromethane. The combined organic phases are dried over sodiumsulfate, concentrated and the residue is chromatographed on a silica gelcolumn (dichloromethane/methanol 30-25:1). Concentration of thechromatographically pure fractions and crystallisation from ethylacetategives 0.17 g of the title compound as a solid of m.p. 191-192° C. Themass spectrum shows the molecular peak MH⁺ at 534.3 Da.

Starting from2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine(starting material A1) and the appropriate boronic acid or boronic acidester derivatives, which can be prepared in a manner known to the personskilled in the art or analogously or similarly as described in theexamples above, such as e.g. in situ from the appropriatebromo-benzenesulfonamide derivatives, the following compounds can beobtained according to the procedures as described by way of example inthe abovementioned examples or analogously or similarly thereto.

29.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-phenethyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C32 H34 N6 O3 S; MW: calc.: 582.73

MS: fnd.: 583.5 (MH⁺)

30.6-[4-(4-Ethyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine

EF: C26 H30 N6 O3 S; MW: calc.: 506.63

MS: fnd.: 507.4 (MH⁺)

31.6-{4-[4-(2,6-Dimethyl-phenyl)-piperazine-1-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine

EF: C32 H34 N3 O3 S; MW: calc.: 582.73

MS: fnd.: 583.5 (MH⁺)

32.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-o-tolyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C31 H32 N6 O3 S; MW: calc.: 568.70

MS: fnd.: 569.4 (MH⁺)

33.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[3-(4-methyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C25 H28 N6 O3 S; MW: calc.: 492.60

MS: fnd.: 493.3 (MH⁺)

34.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(piperidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C25 H27 N5 O3 S; MW: calc.: 477.59

MS: fnd.: 478.3 (MH⁺)

35.4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-phenyl-benzenesulfonamide

EF: C26 H23 N5 O3 S; MW: calc.: 485.57

MS: fnd.: 486.2 (MH⁺)

36.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-methyl-piperazine-1-sulfonyl)-3-trifluoromethoxy-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C26 H27 F3 N6 O4 S; MW: calc.: 576.60

MS: fnd.: 577.3 (MH⁺)

37.6,7-Diethoxy-2-(4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinoline

EF: C33 H35 N5 O5 S; MW: calc.: 613.74

MS: fnd.: 614.3 (MH⁺)

38.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-methyl-piperazine-1-sulfonyl)-3-trifluoromethyl-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C26 H27 F3 N6 O3 S; MW: calc.: 560.60

MS: fnd.: 561.2 (MH⁺)

39.6-[3-Fluoro-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine

EF: C25 H27 F N6 O3 S; MW: calc.: 510.59

MS: fnd.: 511.4 (MH⁺)

40.6-[3-Chloro-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine

EF: C25 H27 Cl N6 O3 S; MW: calc.: 527.05

MS: fnd.: 527.3 (MH⁺)

41.6-[2-Fluoro-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine

EF: C25 H27 F N6 O3 S; MW: calc.: 510.59

MS: fnd.: 511.3 (MH⁺)

42.4-Benzyl-1-(4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyrid-6-yl}-benzenesulfonyl)-[,4]diazepan-5-one

EF: C32 H32 N6 O4 S; MW: calc.: 596.71

MS: fnd.: 597.3 (MH⁺)

43.4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-phenyl-benzenesulfonamide

EF: C27 H25 N5 O3 S; MW: calc.: 499.60

MS: fnd.: 500.20 (MH⁺)

44.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[2-methyl-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C26 H30 N6 O3 S; MW: calc.: 506.63

MS: fnd.: 507.4 (MH⁺)

45.1-(4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-4-methyl-[1,4]diazepan-5-one

EF: C26 H28 N6 O4 S; MW: calc.: 520.61

MS: fnd.: 521.3 (MH⁺)

46.4-Ethyl-1-(4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-[1,4]diazepan-5-one

EF: C27 H30 N6 O4 S; MW: calc.: 534.64

MS: fnd.: 535.3 (MH⁺)

47.4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-o-tolyl-benzenesulfonamide

EF: C27 H25 N5 O3 S; MW: calc.: 499.60

MS: fnd.: 500.2 (MH⁺)

48.4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-pyridin-4-yl-benzenesulfonamide

EF: C26 H24 N6 O3 S; MW: calc.: 500.58

MS: fnd.: 501.3 (MH⁺)

49.4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-p-tolyl-benzenesulfonamide

EF: C28 H27 N5 O3 S; MW: calc.: 513.62

MS: fnd.: 514.3 (MH⁺)

50.N-(4-Dimethylamino-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-benzenesulfonamide

EF: C29 H30 N6 O3 S; MW: calc.: 542.66

MS: fnd.: 543.2 (MH⁺)

51.N-(2-Fluoro-4-methyl-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide

EF: C27 H24 F N5 O3 S; MW: calc.: 517.59

MS: fnd.: 518.2 (MH⁺)

52.N-(4-Methoxy-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide

EF: C27 H25 N5 O4 S; MW: calc.: 515.60

MS: fnd.: 516.3 (MH⁺)

53.N-(4-Methoxy-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-benzenesulfonamide

EF: C28 H27 N5 O4 S; MW: calc.: 529.62

MS: fnd.: 530.2 (MH⁺)

54.4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-o-tolyl-benzenesulfonamide

EF: C28 H27 N5 O3 S; MW: calc.: 513.62

MS: fnd.: 514.2 (MH⁺)

55.N-(4-Chloro-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide

EF: C26 H22 Cl N5 O3 S; MW: calc.: 520.01

MS: fnd.: 520.1 (MH⁺)

56.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(pyrrolidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C24 H25 N5 O3 S; MW: calc.: 463.56

MS: fnd.: 464.3 (MH⁺)

57.6-[4-(Azetidine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine

EF: C23 H23 N5 O3 S; MW: calc.: 449.54

MS: fnd.: 450.2 (MH⁺)

58.N,N-Bis-(2-methoxy-ethyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide

EF: C26 H31 N5 O5 S; MW: calc.: 525.63

MS: fnd.: 526.4 (MH⁺)

59.N-Cyclobutyl-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzene-sulfonamide

EF: C24 H25 N5 O3 S; MW: calc.: 463.56

MS: fnd.: 464.3 (MH⁺)

60.N-Cyclopropyl-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzene-sulfonamide

EF: C23 H23 N5 O3 S; MW: calc.: 449.54

MS: fnd.: 450.2 (MH⁺)

61.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-7-methyl-6-[4-(pyrrolidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C25 H27 N5 O3 S; MW: calc.: 477.59

MS: fnd.: 478.2 (MH⁺)

62.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-7-methyl-6-[4-(pyrrolidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C26 H29 N5 O3 S; MW: calc.: 491.62

MS: fnd.: 492.3 (MH⁺)

63.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-7-methyl-6-[4-(morpholine-4-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C25 H27 N5 O4 S; MW: calc.: 493.59

MS: fnd.: 494.3 (MH⁺)

64.6-[4-(Azetidine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-7-methyl-3H-imidazo-[4,5-b]pyridine

EF: C24 H25 N5 O3 S; MW: calc.: 463.56

MS: fnd.: 464.3 (MH⁺)

65.2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(thiomorpholine-4-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C24 H25 N5 O3 S2; MW: calc.: 495.63

MS: fnd.: 496.3 (MH⁺)

66. 2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(1-oxo-1I(4)-thiomorpholine-4-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine

EF: C24 H25 N5 O4 S2; MW: calc.: 511.63

MS: fnd.: 512.2 (MH⁺)

67.6-[4-(1,1-Dioxo-1I(6)-thiomorpholine-4-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine

EF: C24 H25 N5 O5 S2; MW: calc.: 527.63

MS: fnd.: 528.2 (MH⁺)

68.2-(4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3-H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinoline

EF: C29 H27 N5 O3 S; MW: calc.: 525.63

MS: fnd.:

Starting Materials: A1.2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine

With stirring, a mixture of 8.06 g of 3-(4-methoxypyridin-2-yl)propionicacid (starting material B1), 9.5 g of 2,3-diamino-5-iodopyridine (Cugolaet al., Bioorg. Med. Chem. Lett. 22, 2749-2754 (1996)) and 150 g ofpolyphosphoric acid (PPA) is heated at 140° C. for 22 hours. Aftercooling, the mixture is poured into about 1000 ml of ice-water and thenneutralized (pH 7-8) using 6N aqueous sodium hydroxide solution. Themixture is extracted four times with ethyl acetate and the combinedorganic phases are evaporated to dryness. The residue is crystallizedfirst from ethyl acetate and then from methanol, giving 9.4 g of thetitle compound as a light-beige powder of m.p. 207-208° C.; the massspectrum shows the molecular peak MH⁺ at 381.2 Da.

B1. 3-(4-Methoxypyridin-2-yl)propionic acid

41.95 g of methyl 3-(4-methoxypyridin-2-yl)propionate (starting materialC1) are dissolved in 700 ml of tetrahydrofuran, and 217 ml of 1N sodiumhydroxide solution are added. The mixture is stirred at RT until no morestarting material is detectable (TLC). The mixture is neutralized using217 ml of 1N hydrochloric acid solution, evaporated to dryness and driedunder high vacuum. The colorless residue is ground and extracted fourtimes with dichloromethane/methanol (9:1). The combined extracts areevaporated to dryness. This gives 33.2 g of the title compound as acolorless powder of m.p. 131-132° C. The mass spectrum shows themolecular peak MH⁺ at 182 Da.

C1. Methyl 3-(4-methoxypyridin-2-yl)propionate

43.1 g of methyl 3-(4-methoxypyridin-2-yl)acrylate (starting materialD1) in 600 ml of methanol are hydrogenated over 3.0 g of Pd/C (10%strength) until the starting material has disappeared (TLC). Thecatalyst is filtered off, and the mixture is then concentrated and driedunder high vacuum. This gives 41.95 g of the title compound as alight-yellow oil. The mass spectrum shows the molecular peak MH⁺ at 196Da.

D1. Methyl 3-(4-methoxypyridin-2-yl)acrylate

A mixture of 45 g of 4-methoxypyridine-2-carbaldehyde (Ashimori et al.,Chem. Pharm. Bull. 38, 2446-2458 (1990)), 75.80 g of pyridinehydrochloride, 102.45 g of monomethyl malonate potassium salt and 4.1 mlof piperidine in 700 ml of pyridine are slowly heated, with stirring, to120° C. When the evolution of gas starts, the heating source istemporarily removed to stop the reaction from becoming too violent. Oncethe reaction has subsided, the mixture is stirred at 120° C. for afurther 2.5 hours, and the pyridine is then distilled off under reducedpressure. The residue is partitioned between ethyl acetate/water and theorganic phase is washed with water and dried. The residue obtained afterconcentration is chromatographed on a silica gel column using ethylacetate/petroleum ether 2:1. This initially gives 43.2 g of the titlecompound as a yellow oil which crystallizes on standing and then shows am.p. of 80-82° C. The mass spectrum shows the molecular peak MH⁺ at 194Da.

COMMERCIAL APPLICABILITY

The compounds according to the invention have valuable pharmacologicalproperties which make them commercially utilizable. They are selectiveinhibitors of the enzyme inducible nitric oxide synthase. Nitric oxidesynthases (NO-syntases, NOSs) are enzymes that generate NO andcitrulline from the amino acid arginine. In certain pathophysiologicalsituations such as arginine depletion or tetrahydrobiopterin depletionthe generation of O₂ ⁻ from NO-synthases instead or together with NO hasbeen reported. NO is long known as a signalling molecule in most livingorganisms including mammals and humans. The most prominent action of NOis it's smooth muscle relaxing activity, which is caused on themolecular level by the activation of soluble guanylate cyclase. In thelast years a lot of other enzymes have been shown to be regulated by NOor reaction products of NO. There exist three isoforms of NO-synthaseswhich fall into two classes and differ in their physiologic functionsand molecular properties. The first class, known as constitutiveNO-synthases, comprises of the endothelial NO-synthase and the neuronalNO-synthase. Both isoenzymes are expressed constitutively in variouscell types, but are most prominent in endothelial cells of blood vesselwalls (therefore called endothelial NO-synthase, eNOS or NOS-III) and inneuronal cells (therefore called neuronal NO-synthase, nNOS or NOS-I).Activation of these two enzymes is dependent on Ca²⁺/Calmodulin which isgenerated by transient increases of the intracellular free Ca²⁺concentration. Activation of constitutive isoforms leads to transientbursts of nitric oxide resulting in nanomolar cellular or tissue NOconcentrations. The endothelial isoform is involved in the physiologicregulation of blood pressure. NO generated by the neuronal isoform seemsto have neurotransmitter function and the neuronal isoform is amongother regulatory processes involved in memory function (long termpotentiation).

In contrast to the constitutive isoforms the activation of inducibleNO-synthase (iNOS, NOS-II), the sole member of the second class, isperformed by transcriptional activation of the iNOS-promoter.Proinflammatory stimuli lead to transcription of the gene for inducibleNO-synthase, which is catalytically active without increases in theintracellular Ca²⁺-concentration. Due to the long half live of theinducible NO-synthase and the unregulated activity of the enzyme, highmicromolar concentrations of NO are generated over longer time periods.These high NO-concentrations alone or in cooperation with other reactiveradicals such as O₂ ⁻ are cytotoxic. Therefore, in situations ofmicrobial infections, iNOS is involved in cell killing by macrophagesand other immune cells during early nonspecific immune responses.

There are a number of pathophysiological situations which among othersare characterized by the high expression of inducible NO-synthase andconcomitant high NO or O₂ ⁻ concentrations. It has been shown that thesehigh NO concentrations alone or in combination with other radicalspecies lead to tissue and organ damage and are causally involved inthese pathophysiologies. As inflammation is characterized by theexpression of proinflammatory enzymes, including inducible NO-synthase,acute and chronical inflammatory processes are promising diseases forthe therapeutic application of selective inhibitors of inducibleNO-synthase. Other pathophysiologies with high NO-production frominducible NO-synthase are several forms of shock (septic, hemorrhagicand cytokine-induced). It is clear that nonselective NO-synthaseinhibitors will lead to cardiovascular and neuronal side effects due toconcomitant inhibition of constitutive NO-synthase isoforms.

It has been shown in in-vivo animal models of septic shock thatreduction of circulating plasma NO-levels by NO-scavenger or inhibitionof inducible NO-synthase restores systemic blood pressure, reduces organdamage and increases survival (deAngelo Exp. Opin. Pharmacother. 19-29,1999; Redl et al. Shock 8, Suppl. 51, 1997; Strand at al. Crit. CareMed. 26, 1490-1499, 1998). It has also been shown that increased NOproduction during septic shock contributes to cardiac depression andmyocardial dysfunction (Sun et al. J. Mol. Cell Cardiol. 30, 989-997,1998). Furthermore there are also reports showing reduced infarct sizeafter occlusion of the left anterior coronary artery in the presence ofNO-synthase inhibitors (Wang at al. Am. J. Hyperttens. 12, 174-182,1999). Considerable inducible NO-synthase activity is found in humancardiomyopathy and myocarditis, supporting the hypothesis that NOaccounts at least in part for the dilatation and impaired contractilityin these pathophysiologies (de Belder et al. Br. Heart. J. 4, 426-430,1995).

In animal models of acute or chronic inflammation, blockade of inducibleNO-synthase by isoform-selective or nonselective inhibitors or geneticknock out improves therapeutic outcome. It is reported that experimentalarthritis (Connor et al. Eur. J. Pharmacol. 273, 15-24, 1995) andosteoarthritis (Pelletier et al. Arthritis & Rheum. 41, 1275-1286,1998), experimental inflammations of the gastro-intestinal tract(Zingarelli at al. Gut 45, 199-209, 1999), experimentalglomerulonephritis (Narita et al. Lab. Invest. 72, 17-24, 1995),experimental diabetes (Corbett at al. PNAS 90, 8992-8995, 1993),LPS-induced experimental lung injury is reduced by inhibition ofinducible NO-synthase or in iNOS-knock out mice (Kristof et al. Am. J.Crit. Care. Med. 158, 1883-1889, 1998). A pathophysiological role ofinducible NO-synthase derived NO or O₂ ⁻ is also discussed in chronicinflammatory diseases such as asthma, bronchitis and COPD.

Furthermore, in models of neurodegenerative diseases of the CNS such asMPTP-induced parkinsonism, amyloid peptide induced Alzheimer's disease(Ishii at al., FASEB J. 14, 1485-1489, 2000), malonate inducedHuntington's disease (Connop at al. Neuropharmacol. 35, 459-465, 1996),experimental menengitis (Korytko & Boje Neuropharmacol. 35, 231-237,1996) and experimental encephalitis (Parkinson et al. J. Mol. Med. 75,174-186, 1997) a causal participation of NO and inducible NO-synthasehas been shown.

Increased iNOS expression has been found in the brains of AIDS victimsand it is reasonable to assume a role of iNOS in AIDS related dementia(Bagasra et al. J. Neurovirol. 3 153-167, 1997).

Other studies implicated nitric oxide as a potential mediator ofmicroglia dependent primary demyelination, a hallmark of multiplesklerosis (Parkinson et al. J. Mol. Med. 75, 174-186, 1997).

An inflammatory reaction with concomitant expression of inducibleNO-synthase also takes place during cerebral ischemia and reperfusion(ladecola et al. Stroke 27, 1373-1380, 1996). Resulting NO together withO₂ ⁻ from infiltrating neutrophils is thought to be responsible forcellular and organ damage.

Also, in models of traumatic brain injury (Mesenge et al. J. Neurotrauma13, 209-214, 1996; Wada et al. Neurosurgery 43, 1427-1436, 1998)NO-synthase inhibitors have been show to posses protective properties. Aregulatory role for inducible NO-synthase has been reported in varioustumor cell lines (Tozer & Everett Clin Oncol. 9. 357-264, 1997).

On account of their inducible NO-synthase-inhibiting properties, thecompounds according to the invention can be employed in human andveterinary medicine and therapeutics, where an excess of NO or O₂ ⁻ dueto increases in the activity of inducible NO-synthase is involved. Theycan be used without limitation for the treatment and prophylaxis of thefollowing diseases:

Acute inflammatory diseases: Septic shock, sepsis, SIRS, hemorrhagicshock, shock states induced by cytokine therapy (IL-2, TNF), organtransplantation and transplant rejection, head trauma, acute lunginjury, ARDS, inflammatory skin conditions such as sunburn, inflammatoryeye conditions such as uveitis, glaucoma and conjunctivitis.

Chronic inflammatory diseases of peripheral organs and the CNS:gastrointestinal inflammatory diseases such as Crohn's disease,inflammatory bowel disease, ulcerative colitis, lung inflammatorydiseases such as asthma and COPD, arthritic disorders such as rheumatoidarthritis, osteoarthritis and gouty arthritis, heart disorders such ascardiomyopathy and myocarditis, artherosklerosis, neurogenicinflammation, skin diseases such as psoriasis, dermatitis and eczema,diabetes, glomerulonephritis; dementias such as dementias of theAlzheimer's type, vascular dementia, dementia due to a general medicalcondition, such as AIDS-, Parkinson's disease, Huntington's induceddementias, ALS, multiple sklerosis; necrotizing vasculitides such aspolyarteritis nodosa, serum sickness, Wegener's granulomatosis,Kawasaki's syndrome; headaches such as migraine, chronic tensionheadaches, cluster and vascular headaches, post-traumatic stressdisorders; pain disorders such as neuropathic pain; myocardial andcerebral ischemia/reperfusion injury.

The compounds may also be useful in the treatment of cancers thatexpress nitric oxide synthase.

The invention further relates to a method for the treatment of mammals,including humans, which are suffering from one of the abovementionedillnesses. The method is characterized in that a therapeutically activeand pharmacologically effective and tolerable amount of one or more ofthe compounds according to the invention is administered to the illmammal.

The invention further relates to the compounds according to theinvention for use in the treatment and/or prophylaxis of illnesses,especially the illnesses mentioned.

The invention also relates to the use of the compounds according to theinvention for the production of pharmaceutical compositions which areemployed for the treatment and/or prophylaxis of the illnessesmentioned.

The invention also relates to the use of the compounds according to theinvention for the production of pharmaceutical compositions having aniNOS inhibitory activity.

The invention furthermore relates to pharmaceutical compositions for thetreatment and/or prophylaxis of the illnesses mentioned, which containone or more of the compounds according to the invention.

The invention moreover relates to pharmaceutical compositions accordingto this invention having an iNOS inhibitory activity.

The pharmaceutical compositions are prepared by processes which areknown per se and familiar to the person skilled in the art. Aspharmaceutical compositions, the compounds according to the invention(=active compounds) are either employed as such, or preferably incombination with suitable pharmaceutical auxiliaries and/or excipients,e.g. in the form of tablets, coated tablets, capsules, caplets,suppositories, patches (e.g. as TTS), emulsions, suspensions, gels orsolutions, the active compound content advantageously being between 0.1and 95% and where, by the appropriate choice of the auxiliaries and/orexcipients, a pharmaceutical administration form (e.g. a delayed releaseform or an enteric form) exactly suited to the active compound and/or tothe desired onset of action can be achieved.

The person skilled in the art is familiar with auxiliaries or excipientswhich are suitable for the desired pharmaceutical formulations onaccount of his/her expert knowledge. In addition to solvents, gelformers, ointment bases and other active compound excipients, forexample antioxidants, dispersants, emulsifiers, preservatives,solubilizers, colorants, complexing agents or permeation promoters, canbe used.

The administration of the pharmaceutical compositions according to theinvention may be performed in any of the generally accepted modes ofadministration available in the art. Illustrative examples of suitablemodes of administration include intravenous, oral, nasal, parenteral,topical, transdermal and rectal delivery. Oral and intravenous deliveryare preferred.

For the treatment of disorders of the respiratory tract, the compoundsaccording to the invention are preferably also administered byinhalation in the form of an aerosol; the aerosol particles of solid,liquid or mixed composition preferably having a diameter of 0.5 to 10μm, advantageously of 2 to 6 μm.

Aerosol generation can be carried out, for example, by pressure-drivenjet atomizers or ultrasonic atomizers, but advantageously bypropellant-driven metered aerosols or propellant-free administration ofmicronized active compounds from inhalation capsules.

Depending on the inhaler system used, in addition to the activecompounds the administration forms additionally contain the requiredexcipients, such as, for example, propellants (e.g. Frigen in the caseof metered aerosols), surface-active substances, emulsifiers,stabilizers, preservatives, flavorings, fillers (e.g. lactose in thecase of powder inhalers) or, if appropriate, further active compounds.

For the purposes of inhalation, a large number of apparatuses areavailable with which aerosols of optimum particle size can be generatedand administered, using an inhalation technique which is as right aspossible for the patient. In addition to the use of adaptors (spacers,expanders) and pear-shaped containers (e.g. Nebulator®, Volumatic®), andautomatic devices emitting a puffer spray (Autohaler®), for meteredaerosols, in particular in the case of powder inhalers, a number oftechnical solutions are available (e.g. Diskhaler®, Rotadisk®,Turbohaler® or the inhaler described in European Patent Application EP 0505 321), using which an optimal administration of active compound canbe achieved.

For the treatment of dermatoses, the compounds according to theinvention are in particular administered in the form of thosepharmaceutical compositions which are suitable for topical application.For the production of the pharmaceutical compositions, the compoundsaccording to the invention (=active compounds) are preferably mixed withsuitable pharmaceutical auxiliaries and further processed to givesuitable pharmaceutical formulations. Suitable pharmaceuticalformulations are, for example, powders, emulsions, suspensions, sprays,oils, ointments, fatty ointments, creams, pastes, gels or solutions.

The pharmaceutical compositions according to the invention are preparedby processes known per se. The dosage of the active compounds is carriedout in the order of magnitude customary for iNOS inhibitors. Topicalapplication forms (such as ointments) for the treatment of dermatosesthus contain the active compounds in a concentration of, for example,0.1-99%. The dose for administration by inhalation is customarly between0.1 and 10 mg per day. The customary dose in the case of systemictherapy (p.o.) is between 0.3 and 30 mg/kg per day, (i. v.) is between0.3 and 30 mg/kg/h.

Biological Investigations Measurement of Inducible NO-Synthase Activity

The assay is performed in 96-well microtiter F-plates (Greiner,Frickenhausen, FRG) in a total volume of 100 μl in the presence of 100nM calmodulin, 226 μM CaCl₂, 477 μM MgCl₂, 5 μMflavin-adenine-dinucleotide (FAD), 5 μM flavin mononucleotide (FMN), 0.1mM NADPH, 7 mM glutathione, 10 μM BH4 and 100 mM HEPES pH 7.2. Arginineconcentrations are 0.1 μM for enzyme inhibition experiments. 150000 dpmof [³H]arginine are added to the assay mixture. Enzyme reaction isstarted by the addition of 4 μg of a crude cytosolic fraction containinghuman inducible NO-synthase and the reaction mixture is incubated for 45to 60 min at 37° C. Enzyme reaction is stopped by adding 10 μl of 2MMES-buffer pH 5,0. 50 μl of the incubation mixture are transferred intoa MADP N65 filtration microtiter plate (Millipore, Eschborn, FRG)containing already 50 μl of AG-50W-X8 cation exchange resin (Biorad,München, FRG). The resin in the Na loaded form is pre-equilibrated inwater and 70 μl (corresponding to 50 μl dry beads) are pipetted underheavy stirring with a 8 channel pipette into the filtration plate. Afterpipetting 50 μl of the enzyme reaction mixture onto the filtrationplates, the plates are placed on a filtration manifold (Porvair,Shepperton, UK) and the flow through is collected in Pico scintillationplates (Packard, Meriden, Conn.). The resin in the filtration plates iswashed with 75 μl of water (1×50 μl and 1×25 μl) which is also collectedin the same plate as the sample. The total flow through of 125 μl ismixed with 175 μl of Microscint-40 scintillation cocktail (Packard) andthe scintillation plate is sealed with TopSeal P-foil (Packard).Scintillation plates are counted in a scintillation counter.

For the measurement of inducible NO-synthase-inhibiting potencies ofcompounds increasing concentrations of inhibitors were included into theincubation mixture. IC₅₀-values were calculated from the percentinhibition at given concentrations by nonlinear least square fitting.

The inhibitory values determined for the compounds according to theinvention follow from the following table A, in which the compoundnumbers correspond to the example numbers.

TABLE A Inhibition of iNOS activity [measured as -logIC₅₀ (mol/l)]compound -logIC₅₀ 1 7.71 2 7.45 3 7.84 4 7.52 5 7.58 6 6.90 7 6.51 87.37 9 7.53 10 7.64 11 7.89 12 7.60 13 7.48 14 7.58 15 7.46 16 7.62 177.37 18 7.04 19 7.73 20 7.30 21 6.95 22 7.0 23 7.17 24 7.71 25 7.36 267.46 27 7.34 28 7.41 29 to 68 The inhibitory values of these mentionedExamples lie in the range from 6.43 to 7.85

1.-15. (canceled)
 16. A method for treating an acute inflammatorydisease in a patient comprising administering to said patient atherapeutically effective amount of a compound of formula I

in which R1 is hydrogen or 1-4C-alkyl, R2 is hydrogen or 1-4C-alkyl, andR3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 is 3-7C-cycloalkyl,phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,pyridyl, or R11- and/or R12-substituted phenyl, in which R11 is1-4C-alkyl, halogen, 1-4C-alkoxy, or mono- or di-1-4C-alkylamino, R12 is1-4C-alkyl or halogen, R2 is hydrogen, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 and R2 together andwith inclusion of the nitrogen atom, to which they are bonded, form aheterocyclic ring Het, in which Het is a fully saturated or partiallyunsaturated mono- or fused bicyclic ring or ring system made up of afirst constituent being a 3- to 7-membered monocyclic fully saturatednon-aromatic heterocyclic ring B, which heterocyclic ring B comprisesone to three heteroatoms independently selected from the groupconsisting of nitrogen, oxygen and sulfur, and which heterocyclic ring Bis optionally substituted by one or two oxo groups, and, optionally,fused to said first constituent, a second constituent being a benzenering, and which ring Het is optionally substituted by R21 on a ringcarbon atom, and/or which ring Het is optionally substituted by R22 on afurther ring carbon atom, and/or which ring Het is optionallysubstituted by an ethylenedioxy group, and/or which ring Het isoptionally substituted by R23 on a ring nitrogen atom, in which R21 is1-4C-alkyl, 1-4C-alkoxy or phenylcarbonyl, R22 is 1-4C-alkyl or1-4C-alkoxy, R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,1-4C-alkoxy-2-4C-alkyl, mono- or di-1-4C-alkylamino-2-4C-alkyl, phenyl,pyrimidyl, pyridyl, formyl, 3-7C-cycloalkyl, 3-7C-cycloalkylmethyl, orR231- and/or R232-substituted phenyl, in which R231 is halogen, cyano or1-4C-alkyl, R232 is halogen or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, and in which R4 is hydrogen, halogen,1-4C-alkyl or 1-4C-alkoxy, R5 is 1-4C-alkyl, A is 1-4C-alkylene, or asalt, N-oxide or a salt of an N-oxide thereof.
 17. The method accordingto claim 16, in which R1 is hydrogen or 1-4C-alkyl, R2 is hydrogen or1-4C-alkyl, and R3 is 1-4C-alkyl, trifluoromethyl, or completely orpredominantly fluorine-substituted 1-4C-alkoxy, or in which R1 is3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/or R12-substitutedphenyl, in which R11 is 1-4C-alkyl, halogen, 1-4C-alkoxy, ordi-1-4C-alkylamino, R12 is 1-4C-alkyl or halogen, R2 is hydrogen,hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 ishydrogen, halogen, 1-4C-alkyl, trifluoromethyl, or completely orpredominantly fluorine-substituted 1-4C-alkoxy, or in which R1 and R2together and with inclusion of the nitrogen atom, to which they arebonded, form a heterocyclic ring Het, in which Het is a fully saturatedor partially unsaturated mono- or fused bicyclic ring or ring systemmade up of a first constituent being a 3- to 7-membered monocyclic fullysaturated non-aromatic heterocyclic ring B, which heterocyclic ring B ispiperazine, morpholine, thiomorpholine, homopiperazine, piperidine,pyrrolidine or azetidine, and which heterocyclic ring B is optionallysubstituted by one or two oxo groups, and, optionally, fused to saidfirst constituent, a second constituent being a benzene ring, and whichring Het is optionally substituted by R21 on a ring carbon atom, and/orwhich ring Het is optionally substituted by R22 on a further ring carbonatom, and/or which ring Het is optionally substituted by anethylenedioxy group, and/or which ring Het is optionally substituted byR23 on a ring nitrogen atom, in which R21 is 1-4C-alkyl, 1-4C-alkoxy orphenylcarbonyl, R22 is 1-4C-alkyl or 1-4C-alkoxy, R23 is 1-4C-alkyl,phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,or R231- and/or R232-substituted phenyl, in which R231 is halogen, cyanoor 1-4C-alkyl, R232 is halogen or 1-4C-alkyl, and R3 is hydrogen,halogen, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, and in which R4 is hydrogen, or1-4C-alkyl, R5 is methyl, A is ethylene, or a salt, N-oxide or a salt ofan N-oxide thereof.
 18. The method according to claim 16, in which R1 ishydrogen or 1-4C-alkyl, R2 is hydrogen or 1-4C-alkyl, and R3 is1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 is 3-7C-cycloalkyl,phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,pyridyl, or R11- and/or R12-substituted phenyl, in which R11 is1-4C-alkyl, halogen, 1-4C-alkoxy, or di-1-4C-alkylamino, R12 is1-4C-alkyl or halogen, R2 is hydrogen, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 and R2 together andwith inclusion of the nitrogen atom, to which they are bonded, form aheterocyclic ring Het, in which Het is piperidinyl, pyrrolidinyl,azetidinyl, morpholinyl, thiomorpholinyl, S-oxo-thiomorpholinyl,S,S-dioxo-thiomorpholinyl, 1,2,3,4-tetrahydroisoquinolinyl,di-(1-4C-alkoxy)-1,2,3,4-tetrahydroisoquinolinyl, piperidinylsubstituted by either ethylenedioxy or R21, 4N—(R23)-piperazinyl,4N—(R23)-homopiperazinyl, 4N—(H)-1,4-diazepan-5-one-1-yl or4N—(R23)-1,4-diazepan-5-one-1-yl, in which R21 is 1-4C-alkyl, orphenylcarbonyl, R23 is 1-4C-alkyl, phenyl-1-4C-alkyl,1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/orR232-substituted phenyl, in which R231 is halogen, cyano or 1-4C-alkyl,R232 is halogen or 1-4C-alkyl, and R3 is hydrogen, halogen, 1-4C-alkyl,trifluoromethyl, or completely or predominantly fluorine-substituted1-4C-alkoxy, and in which R4 is hydrogen, or 1-4C-alkyl, R5 is methyl, Ais ethylene, or a salt, N-oxide or a salt of an N-oxide thereof.
 19. Themethod according to claim 16, in which R1 is hydrogen or 1-4C-alkyl, R2is hydrogen or 1-4C-alkyl, and R3 is 1-4C-alkyl, trifluoromethyl, orcompletely or predominantly fluorine-substituted 1-4C-alkoxy, or inwhich R1 is 3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/or R12-substitutedphenyl, in which either R11 is 1-4C-alkyl, 1-4C-alkoxy, ordi-1-4C-alkylamino, and R12 is halogen, or R11 is halogen, 1-4C-alkoxy,or di-1-4C-alkylamino, and R12 is 1-4C-alkyl, R2 is hydrogen,hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 ishydrogen, or in which R1 and R2 together and with inclusion of thenitrogen atom, to which they are bonded, form a heterocyclic ring Het,in which Het is piperidinyl, pyrrolidinyl, azetidinyl, morpholinyl,thiomorpholinyl, S-oxo-thiomorpholinyl, S,S-dioxo-thiomorpholinyl,1,2,3,4-tetrahydroisoquinolinyl,di-(1-4C-alkoxy)-1,2,3,4-tetrahydroisoquinolinyl, piperidinylsubstituted by either ethylenedioxy or R21, 4N—(R23)-piperazinyl,4N—(1-4C-alkyl)-homopiperazinyl, 4N—(H)-1,4-diazepan-5-one-1-yl,4N—(phenyl-1-4C-alkyl)-1,4-diazepan-5-one-1-yl or4N—(1-4C-alkyl)-1,4-diazepan-5-one-1-yl, in which R21 is 1-4C-alkyl, orphenylcarbonyl, R23 is 1-4C-alkyl, phenyl-1-4C-alkyl,1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/orR232-substituted phenyl, in which R231 is halogen, cyano or 1-4C-alkyl,R232 is halogen or 1-4C-alkyl, and R3 is hydrogen, halogen, 1-4C-alkyl,trifluoromethyl, or completely or predominantly fluorine-substituted1-4C-alkoxy, and in which R4 is hydrogen, or 1-4C-alkyl, R5 is methyl, Ais ethylene, or a salt, N-oxide or a salt of an N-oxide thereof.
 20. Themethod according to claim 16, in which R1 is methyl, R2 is methyl, andR3 is methyl, trifluoromethyl, or trifluoromethoxy, or in which R1 iscyclohexyl, cyclobutyl, cyclopropyl, benzyl, 2-hydroxy-ethyl,2-methoxy-ethyl, phenyl, pyridyl, or R11- and/or R12-substituted phenyl,in which either R11 is methyl, methoxy, or dimethylamino, and R12 isfluorine, or R11 is fluorine, chlorine, methoxy, or dimethylamino, andR12 is methyl, R2 is hydrogen, 2-hydroxy-ethyl, 2-methoxy-ethyl, ormethyl, and R3 is hydrogen, or in which R1 and R2 together and withinclusion of the nitrogen atom, to which they are bonded, form aheterocyclic ring Het, in which Het is piperidinyl, pyrrolidinyl,azetidinyl, or morpholinyl, thiomorpholinyl, S-oxo-thiomorpholinyl,S,S-dioxo-thiomorpholinyl, 1,2,3,4-tetrahydroisoquinolinyl,di-methoxy-1,2,3,4-tetrahydroisoquinolinyl,di-ethoxy-1,2,3,4-tetrahydroisoquinolinyl,4,4-ethylenedioxy-piperidinyl, 4-(R21)-piperidinyl,4N—(R23)-piperazinyl, 4N-methyl-homopiperazinyl,4N—(H)-1,4-diazepan-5-one-1-yl, 4N-benzyl-1,4-diazepan-5-one-1-yl,4N-methyl-1,4-diazepan-5-one-1-yl, or 4N-ethyl-1,4-diazepan-5-one-1-yl,in which R21 is methyl, or phenylcarbonyl, R23 is methyl, ethyl, benzyl,phenethyl, acetyl, 2-methoxy-ethyl, phenyl, or R231- and/orR232-substituted phenyl, in which either R231 is chlorine, cyano ormethyl, and R232 is chlorine, or R231 is chlorine, cyano or methyl, andR232 is methyl, and R3 is hydrogen, fluorine, chlorine, methyl,trifluoromethyl, or trifluoromethoxy, and in which R4 is hydrogen, ormethyl, R5 is methyl, A is ethylene, or a salt, N-oxide or a salt of anN-oxide thereof.
 21. The method according to claim 16, in which R1 ishydrogen or 1-4C-alkyl, R2 is hydrogen or 1-4C-alkyl, and R3 is1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or R1 is 3-7C-cycloalkyl,phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,pyridyl, or R11- and/or R12-substituted phenyl, in which R11 is1-4C-alkyl, halogen, 1-4C-alkoxy, or mono- or di-1-4C-alkylamino, R12 is1-4C-alkyl or halogen, R2 is hydrogen, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or R1 and R2 together and withinclusion of the nitrogen atom, to which they are bonded, form aheterocyclic ring Het, in which Het is a 3- to 10-membered saturated orpartially saturated heterocyclic ring comprising totally 1 to 3heteroatoms selected from the group consisting of oxygen, sulfur andnitrogen, and optionally substituted by R21 on a ring carbon atom and/orby R22 on a further ring carbon atom and/or by R23 on a ring nitrogenatom, in which R21 is 1-4C-alkyl, 1-4C-alkoxy or phenylcarbonyl, R22 is1-4C-alkyl or 1-4C-alkoxy, R23 is 1-4C-alkyl, phenyl-1-4C-alkyl,1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, mono- ordi-1-4C-alkylamino-2-4C-alkyl, phenyl, pyrimidyl, pyridyl, formyl,3-7C-cycloalkyl, 3-7C-cycloalkylmethyl, or R231- and/or R232-substitutedphenyl, in which R231 is halogen, cyano or 1-4C-alkyl, R232 is halogenor 1-4C-alkyl, and R3 is hydrogen, halogen, 1-4C-alkoxy, 1-4C-alkyl,trifluoromethyl, or completely or predominantly fluorine-substituted1-4C-alkoxy, R4 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy, R5 is1-4C-alkyl, A is 1-4C-alkylene, or a salt, N-oxide or a salt of anN-oxide thereof.
 22. The method according to claim 16, in which R1 ishydrogen or 1-4C-alkyl, R2 is hydrogen or 1-4C-alkyl, and R3 is1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or R1 is 3-7C-cycloalkyl,phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/orR12-substituted phenyl, in which either R11 is 1-4C-alkyl, 1-4C-alkoxy,or mono- or di-1-4C-alkylamino, and R12 is halogen, or R11 is halogen,1-4C-alkoxy, or mono- or di-1-4C-alkylamino, and R12 is 1-4C-alkyl, R2is hydrogen, hydroxy-2-4C-alkyl or 1-4C-alkyl, and R3 is hydrogen,halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely orpredominantly fluorine-substituted 1-4C-alkoxy, or R1 and R2 togetherand with inclusion of the nitrogen atom, to which they are bonded, forma heterocyclic ring Het, in which Het is optionally substituted by R21on a ring carbon atom and/or by R22 on a further ring carbon atom and/orby R23 on a ring nitrogen atom and is azetidin-1-yl, pyrrolidin-1-yl,piperazin-1-yl, thiomorpholin-4-yl, homopiperidin-1-yl,homopiperazin-1-yl, indolin-1-yl, isoindolin-1-yl,1,2,3,4-tetrahydroquinolin-2-yl, piperidin-1-yl, morpholin-4-yl,1,2,3,4-tetrahydroisoquinolin-1-yl, 1,4-diazepan-5-one-1-yl, or1,4-dioxa-8-azaspiro[4,5]decan-8-yl, in which R21 is 1-4C-alkyl,1-4C-alkoxy or phenylcarbonyl, R22 is 1-4C-alkoxy, R23 is 1-4C-alkyl,phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,or R231- and/or R232-substituted phenyl, in which R231 is halogen, cyanoor 1-4C-alkyl, R232 is halogen or 1-4C-alkyl, and R3 is hydrogen,halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely orpredominantly fluorine-substituted 1-4C-alkoxy, R4 is hydrogen, R5 ismethyl, A is ethylene, or a salt, N-oxide or a salt of an N-oxidethereof.
 23. The method according to claim 16, in which R1 is methyl, R2is methyl, and R3 is methyl, trifluoromethyl or trifluoromethoxy, or R1is cyclohexyl, benzyl, 2-hydroxyethyl, phenyl, pyridyl, or R11- and/orR12-substituted phenyl, in which either R11 is methyl, methoxy ordimethylamino, and R12 is chlorine or fluorine, or R11 is chlorine,fluorine, methoxy or dimethylamino, and R12 is methyl, R2 is hydrogen ormethyl, or R1 and R2 are both 2-hydroxyethyl, and R3 is hydrogen, or R1and R2 together and with inclusion of the nitrogen atom, to which theyare bonded, form a heterocyclic ring Het, in which Het ispiperidin-1-yl, or piperidin-1-yl substituted by R21, in which R21 ismethyl or phenylcarbonyl, or Het is 1,2,3,4-tetrahydroisoquinolin-2-ylsubstituted by R21 and R22, in which R21 is methoxy, R22 is methoxy, orHet is piperazin-1-yl substituted by R23 on 4-N, in which R23 is methyl,ethyl, benzyl, phenethyl, acetyl, 2-methoxyethyl, phenyl, or R231-and/or R232-substituted phenyl, in which R231 is chlorine, cyano ormethyl, R232 is chlorine or methyl, or Het is 1,4-diazepan-5-one-1-yl,or 1,4-diazepan-5-one-1-yl substituted by R23 on 4-N, in which R23 ismethyl, ethyl or benzyl, or Het is homopiperazin-1-yl substituted by R23on 4-N, in which R23 is methyl, or Het is morpholin-4-yl, azetidin-1-yl,pyrrolidin-1-yl, or 1,4-dioxa-8-azaspiro[4,5]decan-8-yl, and R3 ishydrogen, fluorine, chlorine, methyl, trifluoromethyl ortrifluoromethoxy, R4 is hydrogen, R5 is methyl, A is ethylene, or asalt, N-oxide or a salt of an N-oxide thereof.
 24. The method accordingto claim 16, in which the compound is selected from the group consistingof2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-methylpiperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-benzylpiperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-phenylpiperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-{4-[4-(4-cyanophenyl)-piperazin-1-yl-sulfonyl]-phenyl}-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-p-tolyl-piperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;6-{4-[4-(2,4-Dimethylphenyl)-piperazin-1-yl-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-{4-[4-(3,5-Dichlorphenyl)-piperazin-1-yl-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-{4-[4-(2-Methoxy-ethyl)-piperazin-1-yl-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-[4-(4-Acetyl-piperazin-1-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(morpholin-4-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-methyl-[1,4]diazepan-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-methyl-piperidin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;6-[4-(4-Benzoyl-piperidin-1-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-[4-(1,4-dioxa-8-azaspiro[4,5]decan-8-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-[4-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-[4-(1,4-Diazepan-5-one-1-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;N—(2-Hydroxyethyl)-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;N,N-Bis-(2-hydroxyethyl)-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;N-Benzyl-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;N-Cyclohexyl-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N,N-dimethyl-2-trifluormethoxy-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N,N-dimethyl-2-trifluormethyl-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N,N-dimethyl-3-methyl-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-phenyl-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-p-tolyl-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-(2-methoxyphenyl)-benzenesulfonamide;N-(4-Dimethylamino-phenyl)-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}-benzenesulfonamid;N-(4-Chlorphenyl)-N-methyl-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-phenethyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;6-[4-(4-Ethyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;6-{4-[4-(2,6-Dimethyl-phenyl)-piperazine-1-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-o-tolyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[3-(4-methyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(piperidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-phenyl-benzenesulfonamide;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-methyl-piperazine-1-sulfonyl)-3-trifluoromethoxy-phenyl]-3H-imidazo[4,5-b]pyridine;6,7-Diethoxy-2-(4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinoline;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-methyl-piperazine-1-sulfonyl)-3-trifluoromethyl-phenyl]-3H-imidazo[4,5-b]pyridine;6-[3-Fluoro-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;6-[3-Chloro-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;6-[2-Fluoro-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;4-Benzyl-1-(4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-[1,4]diazepan-5-one;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-phenyl-benzenesulfonamide;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[2-methyl-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;1-(4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-4-methyl-[1,4]diazepan-5-one;4-Ethyl-1-(4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-[1,4]diazepan-5-one;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-o-tolyl-benzenesulfonamide;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-pyridin-4-yl-benzenesulfonamide;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-p-tolyl-benzenesulfonamide;N—(4-Dimethylamino-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-benzenesulfonamide;N-(2-Fluoro-4-methyl-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide;N-(4-Methoxy-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide;N-(4-Methoxy-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-benzenesulfonamide;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-o-tolyl-benzenesulfonamide;N-(4-Chloro-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(pyrrolidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;6-[4-(Azetidine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;N,N-Bis-(2-methoxy-ethyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide;N-Cyclobutyl-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzene-sulfonamide;N-Cyclopropyl-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzene-sulfonamide;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-7-methyl-6-[4-(pyrrolidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-7-methyl-6-[4-(piperidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-7-methyl-6-[4-(morpholine-4-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;6-[4-(Azetidine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-7-methyl-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(thiomorpholine-4-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(1-oxo-1I(4)-thiomorpholine-4-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;6-[4-(1,1-Dioxo-1I(6)-thiomorpholine-4-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;2-(4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3-H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinoline,and the salts, N-oxides and the salts of the N-oxides thereof.
 25. Amethod for treating a chronic inflammatory disease of peripheral organsand the central nervous system (CNS) in a patient comprisingadministering to said patient a therapeutically effective amount of acompound of formula I compound of formula I

in which R1 is hydrogen or 1-4C-alkyl, R2 is hydrogen or 1-4C-alkyl, andR3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 is 3-7C-cycloalkyl,phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,pyridyl, or R11- and/or R12-substituted phenyl, in which R11 is1-4C-alkyl, halogen, 1-4C-alkoxy, or mono- or di-1-4C-alkylamino, R12 is1-4C-alkyl or halogen, R2 is hydrogen, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 and R2 together andwith inclusion of the nitrogen atom, to which they are bonded, form aheterocyclic ring Het, in which Het is a fully saturated or partiallyunsaturated mono- or fused bicyclic ring or ring system made up of afirst constituent being a 3- to 7-membered monocyclic fully saturatednon-aromatic heterocyclic ring B, which heterocyclic ring B comprisesone to three heteroatoms independently selected from the groupconsisting of nitrogen, oxygen and sulfur, and which heterocyclic ring Bis optionally substituted by one or two oxo groups, and, optionally,fused to said first constituent, a second constituent being a benzenering, and which ring Het is optionally substituted by R21 on a ringcarbon atom, and/or which ring Het is optionally substituted by R22 on afurther ring carbon atom, and/or which ring Het is optionallysubstituted by an ethylenedioxy group, and/or which ring Het isoptionally substituted by R23 on a ring nitrogen atom, in which R21 is1-4C-alkyl, 1-4C-alkoxy or phenylcarbonyl, R22 is 1-4C-alkyl or1-4C-alkoxy, R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,1-4C-alkoxy-2-4C-alkyl, mono- or di-1-4C-alkylamino-2-4C-alkyl, phenyl,pyrimidyl, pyridyl, formyl, 3-7C-cycloalkyl, 3-7C-cycloalkylmethyl, orR231- and/or R232-substituted phenyl, in which R231 is halogen, cyano or1-4C-alkyl, R232 is halogen or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, and in which R4 is hydrogen, halogen,1-4C-alkyl or 1-4C-alkoxy, R5 is 1-4C-alkyl, A is 1-4C-alkylene, or asalt, N-oxide or a salt of an N-oxide thereof.
 26. The method accordingto claim 25, in which R1 is hydrogen or 1-4C-alkyl, R2 is hydrogen or1-4C-alkyl, and R3 is 1-4C-alkyl, trifluoromethyl, or completely orpredominantly fluorine-substituted 1-4C-alkoxy, or in which R1 is3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/or R12-substitutedphenyl, in which R11 is 1-4C-alkyl, halogen, 1-4C-alkoxy, ordi-1-4C-alkylamino, R12 is 1-4C-alkyl or halogen, R2 is hydrogen,hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 ishydrogen, halogen, 1-4C-alkyl, trifluoromethyl, or completely orpredominantly fluorine-substituted 1-4C-alkoxy, or in which R1 and R2together and with inclusion of the nitrogen atom, to which they arebonded, form a heterocyclic ring Het, in which Het is a fully saturatedor partially unsaturated mono- or fused bicyclic ring or ring systemmade up of a first constituent being a 3- to 7-membered monocyclic fullysaturated non-aromatic heterocyclic ring B, which heterocyclic ring B ispiperazine, morpholine, thiomorpholine, homopiperazine, piperidine,pyrrolidine or azetidine, and which heterocyclic ring B is optionallysubstituted by one or two oxo groups, and, optionally, fused to saidfirst constituent, a second constituent being a benzene ring, and whichring Het is optionally substituted by R21 on a ring carbon atom, and/orwhich ring Het is optionally substituted by R22 on a further ring carbonatom, and/or which ring Het is optionally substituted by anethylenedioxy group, and/or which ring Het is optionally substituted byR23 on a ring nitrogen atom, in which R21 is 1-4C-alkyl, 1-4C-alkoxy orphenylcarbonyl, R22 is 1-4C-alkyl or 1-4C-alkoxy, R23 is 1-4C-alkyl,phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,or R231- and/or R232-substituted phenyl, in which R231 is halogen, cyanoor 1-4C-alkyl, R232 is halogen or 1-4C-alkyl, and R3 is hydrogen,halogen, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, and in which R4 is hydrogen, or1-4C-alkyl, R5 is methyl, A is ethylene, or a salt, N-oxide or a salt ofan N-oxide thereof.
 27. The method according to claim 25, in which R1 ishydrogen or 1-4C-alkyl, R2 is hydrogen or 1-4C-alkyl, and R3 is1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 is 3-7C-cycloalkyl,phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,pyridyl, or R11- and/or R12-substituted phenyl, in which R11 is1-4C-alkyl, halogen, 1-4C-alkoxy, or di-1-4C-alkylamino, R12 is1-4C-alkyl or halogen, R2 is hydrogen, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 and R2 together andwith inclusion of the nitrogen atom, to which they are bonded, form aheterocyclic ring Het, in which Het is piperidinyl, pyrrolidinyl,azetidinyl, morpholinyl, thiomorpholinyl, S-oxo-thiomorpholinyl,S,S-dioxo-thiomorpholinyl, 1,2,3,4-tetrahydroisoquinolinyl,di-(1-4C-alkoxy)-1,2,3,4-tetrahydroisoquinolinyl, piperidinylsubstituted by either ethylenedioxy or R21, 4N—(R23)-piperazinyl,4N—(R23)-homopiperazinyl, 4N—(H)-1,4-diazepan-5-one-1-yl or4N—(R23)-1,4-diazepan-5-one-1-yl, in which R21 is 1-4C-alkyl, orphenylcarbonyl, R23 is 1-4C-alkyl, phenyl-1-4C-alkyl,1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/orR232-substituted phenyl, in which R231 is halogen, cyano or 1-4C-alkyl,R232 is halogen or 1-4C-alkyl, and R3 is hydrogen, halogen, 1-4C-alkyl,trifluoromethyl, or completely or predominantly fluorine-substituted1-4C-alkoxy, and in which R4 is hydrogen, or 1-4C-alkyl, R5 is methyl, Ais ethylene, or a salt, N-oxide or a salt of an N-oxide thereof.
 28. Themethod according to claim 25, in which R1 is hydrogen or 1-4C-alkyl, R2is hydrogen or 1-4C-alkyl, and R3 is 1-4C-alkyl, trifluoromethyl, orcompletely or predominantly fluorine-substituted 1-4C-alkoxy, or inwhich R1 is 3-7C-cycloalkyl, phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/or R12-substitutedphenyl, in which either R11 is 1-4C-alkyl, 1-4C-alkoxy, ordi-1-4C-alkylamino, and R12 is halogen, or R11 is halogen, 1-4C-alkoxy,or di-1-4C-alkylamino, and R12 is 1-4C-alkyl, R2 is hydrogen,hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 ishydrogen, or in which R1 and R2 together and with inclusion of thenitrogen atom, to which they are bonded, form a heterocyclic ring Het,in which Het is piperidinyl, pyrrolidinyl, azetidinyl, morpholinyl,thiomorpholinyl, S-oxo-thiomorpholinyl, S,S-dioxo-thiomorpholinyl,1,2,3,4-tetrahydroisoquinolinyl,di-(1-4C-alkoxy)-1,2,3,4-tetrahydroisoquinolinyl, piperidinylsubstituted by either ethylenedioxy or R21, 4N—(R23)-piperazinyl,4N-(1-4C-alkyl)-homopiperazinyl, 4N—(H)-1,4-diazepan-5-one-1-yl,4N-(phenyl-1-4C-alkyl)-1,4-diazepan-5-one-1-yl or4N-(1-4C-alkyl)-1,4-diazepan-5-one-1-yl, in which R21 is 1-4C-alkyl, orphenylcarbonyl, R23 is 1-4C-alkyl, phenyl-1-4C-alkyl,1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, phenyl, or R231- and/orR232-substituted phenyl, in which R231 is halogen, cyano or 1-4C-alkyl,R232 is halogen or 1-4C-alkyl, and R3 is hydrogen, halogen, 1-4C-alkyl,trifluoromethyl, or completely or predominantly fluorine-substituted1-4C-alkoxy, and in which R4 is hydrogen, or 1-4C-alkyl, R5 is methyl, Ais ethylene, or a salt, N-oxide or a salt of an N-oxide thereof.
 29. Themethod according to claim 25, in which R1 is methyl, R2 is methyl, andR3 is methyl, trifluoromethyl, or trifluoromethoxy, or in which R1 iscyclohexyl, cyclobutyl, cyclopropyl, benzyl, 2-hydroxy-ethyl,2-methoxy-ethyl, phenyl, pyridyl, or R11- and/or R12-substituted phenyl,in which either R11 is methyl, methoxy, or dimethylamino, and R12 isfluorine, or R11 is fluorine, chlorine, methoxy, or dimethylamino, andR12 is methyl, R2 is hydrogen, 2-hydroxy-ethyl, 2-methoxy-ethyl, ormethyl, and R3 is hydrogen, or in which R1 and R2 together and withinclusion of the nitrogen atom, to which they are bonded, form aheterocyclic ring Het, in which Het is piperidinyl, pyrrolidinyl,azetidinyl, or morpholinyl, thiomorpholinyl, S-oxo-thiomorpholinyl,S,S-dioxo-thiomorpholinyl, 1,2,3,4-tetrahydroisoquinolinyl,di-methoxy-1,2,3,4-tetrahydroisoquinolinyl,di-ethoxy-1,2,3,4-tetrahydroisoquinolinyl,4,4-ethylenedioxy-piperidinyl, 4-(R21)-piperidinyl,4N—(R23)-piperazinyl, 4N-methyl-homopiperazinyl,4N—(H)-1,4-diazepan-5-one-1-yl, 4N-benzyl-1,4-diazepan-5-one-1-yl,4N-methyl-1,4-diazepan-5-one-1-yl, or 4N-ethyl-1,4-diazepan-5-one-1-yl,in which R21 is methyl, or phenylcarbonyl, R23 is methyl, ethyl, benzyl,phenethyl, acetyl, 2-methoxy-ethyl, phenyl, or R231- and/orR232-substituted phenyl, in which either R231 is chlorine, cyano ormethyl, and R232 is chlorine, or R231 is chlorine, cyano or methyl, andR232 is methyl, and R3 is hydrogen, fluorine, chlorine, methyl,trifluoromethyl, or trifluoromethoxy, and in which R4 is hydrogen, ormethyl, R5 is methyl, A is ethylene, or a salt, N-oxide or a salt of anN-oxide thereof.
 30. The method according to claim 25, in which R1 ishydrogen or 1-4C-alkyl, R2 is hydrogen or 1-4C-alkyl, and R3 is1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or R1 is 3-7C-cycloalkyl,phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,pyridyl, or R11- and/or R12-substituted phenyl, in which R11 is1-4C-alkyl, halogen, 1-4C-alkoxy, or mono- or di-1-4C-alkylamino, R12 is1-4C-alkyl or halogen, R2 is hydrogen, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or R1 and R2 together and withinclusion of the nitrogen atom, to which they are bonded, form aheterocyclic ring Het, in which Het is a 3- to 10-membered saturated orpartially saturated heterocyclic ring comprising totally 1 to 3heteroatoms selected from the group consisting of oxygen, sulfur andnitrogen, and optionally substituted by R21 on a ring carbon atom and/orby R22 on a further ring carbon atom and/or by R23 on a ring nitrogenatom, in which R21 is 1-4C-alkyl, 1-4C-alkoxy or phenylcarbonyl, R22 is1-4C-alkyl or 1-4C-alkoxy, R23 is 1-4C-alkyl, phenyl-1-4C-alkyl,1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, mono- ordi-1-4C-alkylamino-2-4C-alkyl, phenyl, pyrimidyl, pyridyl, formyl,3-7C-cycloalkyl, 3-7C-cycloalkylmethyl, or R231- and/or R232-substitutedphenyl, in which R231 is halogen, cyano or 1-4C-alkyl, R232 is halogenor 1-4C-alkyl, and R3 is hydrogen, halogen, 1-4C-alkoxy, 1-4C-alkyl,trifluoromethyl, or completely or predominantly fluorine-substituted1-4C-alkoxy, R4 is hydrogen, halogen, 1-4C-alkyl or 1-4C-alkoxy, R5 is1-4C-alkyl, A is 1-4C-alkylene, or a salt, N-oxide or a salt of anN-oxide thereof.
 31. The method according to claim 25, in which R1 ishydrogen or 1-4C-alkyl, R2 is hydrogen or 1-4C-alkyl, and R3 is1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or R1 is 3-7C-cycloalkyl,phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl, phenyl, pyridyl, or R11- and/orR12-substituted phenyl, in which either R11 is 1-4C-alkyl, 1-4C-alkoxy,or mono- or di-1-4C-alkylamino, and R12 is halogen, or R11 is halogen,1-4C-alkoxy, or mono- or di-1-4C-alkylamino, and R12 is 1-4C-alkyl, R2is hydrogen, hydroxy-2-4C-alkyl or 1-4C-alkyl, and R3 is hydrogen,halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely orpredominantly fluorine-substituted 1-4C-alkoxy, or R1 and R2 togetherand with inclusion of the nitrogen atom, to which they are bonded, forma heterocyclic ring Het, in which Het is optionally substituted by R21on a ring carbon atom and/or by R22 on a further ring carbon atom and/orby R23 on a ring nitrogen atom and is azetidin-1-yl, pyrrolidin-1-yl,piperazin-1-yl, thiomorpholin-4-yl, homopiperidin-1-yl,homopiperazin-1-yl, indolin-1-yl, isoindolin-1-yl,1,2,3,4-tetrahydroquinolin-2-yl, piperidin-1-yl, morpholin-4-yl,1,2,3,4-tetrahydroisoquinolin-1-yl, 1,4-diazepan-5-one-1-yl, or1,4-dioxa-8-azaspiro[4,5]decan-8-yl, in which R21 is 1-4C-alkyl,1-4C-alkoxy or phenylcarbonyl, R22 is 1-4C-alkoxy, R23 is 1-4C-alkyl,phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,or R231- and/or R232-substituted phenyl, in which R231 is halogen, cyanoor 1-4C-alkyl, R232 is halogen or 1-4C-alkyl, and R3 is hydrogen,halogen, 1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely orpredominantly fluorine-substituted 1-4C-alkoxy, R4 is hydrogen, R5 ismethyl, A is ethylene, or a salt, N-oxide or a salt of an N-oxidethereof.
 32. The method according to claim 25, in which R1 is methyl, R2is methyl, and R3 is methyl, trifluoromethyl or trifluoromethoxy, or R1is cyclohexyl, benzyl, 2-hydroxyethyl, phenyl, pyridyl, or R11- and/orR12-substituted phenyl, in which either R11 is methyl, methoxy ordimethylamino, and R12 is chlorine or fluorine, or R11 is chlorine,fluorine, methoxy or dimethylamino, and R12 is methyl, R2 is hydrogen ormethyl, or R1 and R2 are both 2-hydroxyethyl, and R3 is hydrogen, or R1and R2 together and with inclusion of the nitrogen atom, to which theyare bonded, form a heterocyclic ring Het, in which Het ispiperidin-1-yl, or piperidin-1-yl substituted by R21, in which R21 ismethyl or phenylcarbonyl, or Het is 1,2,3,4-tetrahydroisoquinolin-2-ylsubstituted by R21 and R22, in which R21 is methoxy, R22 is methoxy, orHet is piperazin-1-yl substituted by R23 on 4-N, in which R23 is methyl,ethyl, benzyl, phenethyl, acetyl, 2-methoxyethyl, phenyl, or R231-and/or R232-substituted phenyl, in which R231 is chlorine, cyano ormethyl, R232 is chlorine or methyl, or Het is 1,4-diazepan-5-one-1-yl,or 1,4-diazepan-5-one-1-yl substituted by R23 on 4-N, in which R23 ismethyl, ethyl or benzyl, or Het is homopiperazin-1-yl substituted by R23on 4-N, in which R23 is methyl, or Het is morpholin-4-yl, azetidin-1-yl,pyrrolidin-1-yl, or 1,4-dioxa-8-azaspiro[4,5]decan-8-yl, and R3 ishydrogen, fluorine, chlorine, methyl, trifluoromethyl ortrifluoromethoxy, R4 is hydrogen, R5 is methyl, A is ethylene, or asalt, N-oxide or a salt of an N-oxide thereof.
 33. The method accordingto claim 25, in which the compound is selected from the group consistingof2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-methylpiperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-benzylpiperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-phenylpiperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-{-4-[4-(4-cyanophenyl)-piperazin-1-yl-sulfonyl]-phenyl}-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-p-tolyl-piperazin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;6-{4-[4-(2,4-Dimethylphenyl)-piperazin-1-yl-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-{4-[4-(3,5-Dichlorphenyl)-piperazin-1-yl-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-{4-[4-(2-Methoxy-ethyl)-piperazin-1-yl-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-[4-(4-Acetyl-piperazin-1-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(morpholin-4-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-methyl-[1,4]diazepan-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxypyridin-2-yl)ethyl]-6-[4-(4-methyl-piperidin-1-yl-sulfonyl)-phenyl]-3H-imidazo-[4,5-b]pyridine;6-[4-(4-Benzoyl-piperidin-1-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-[4-(1,4-dioxa-8-azaspiro[4,5]decan-8-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-[4-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;6-[4-(1,4-Diazepan-5-one-1-yl-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridine;N-(2-Hydroxyethyl)-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;N,N-Bis-(2-hydroxyethyl)-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;N-Benzyl-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;N-Cyclohexyl-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N,N-dimethyl-2-trifluormethoxy-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N,N-dimethyl-2-trifluormethyl-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N,N-dimethyl-3-methyl-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-phenyl-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-p-tolyl-benzenesulfonamide;4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-(2-methoxyphenyl)-benzenesulfonamide;N-(4-Dimethylamino-phenyl)-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}-benzenesulfonamid;N-(4-Chlorphenyl)-N-methyl-4-{2-[2-(4-methoxypyridin-2-yl)ethyl]-3H-imidazo-[4,5-b]pyridin-6-yl}benzenesulfonamid;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-phenethyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;6-[4-(4-Ethyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;6-{4-[4-(2,6-Dimethyl-phenyl)-piperazine-1-sulfonyl]-phenyl}-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-o-tolyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[3-(4-methyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(piperidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-phenyl-benzenesulfonamide;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-methyl-piperazine-1-sulfonyl)-3-trifluoromethoxy-phenyl]-3H-imidazo[4,5-b]pyridine;6,7-Diethoxy-2-(4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinoline;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(4-methyl-piperazine-1-sulfonyl)-3-trifluoromethyl-phenyl]-3H-imidazo[4,5-b]pyridine;6-[3-Fluoro-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;6-[3-Chloro-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;6-[2-Fluoro-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;4-Benzyl-1-(4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-[1,4]diazepan-5-one;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-phenyl-benzenesulfonamide;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[2-methyl-4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;1-(4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-4-methyl-[1,4]diazepan-5-one;4-Ethyl-1-(4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-[1,4]diazepan-5-one;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-o-tolyl-benzenesulfonamide;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-pyridin-4-yl-benzenesulfonamide;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-p-tolyl-benzenesulfonamide;N-(4-Dimethylamino-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-benzenesulfonamide;N-(2-Fluoro-4-methyl-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide;N-(4-Methoxy-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide;N-(4-Methoxy-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-benzenesulfonamide;4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-N-o-tolyl-benzenesulfonamide;N-(4-Chloro-phenyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(pyrrolidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;6-[4-(Azetidine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;N,N-Bis-(2-methoxy-ethyl)-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonamide;N-Cyclobutyl-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzene-sulfonamide;N-Cyclopropyl-4-{2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-benzene-sulfonamide;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-7-methyl-6-[4-(pyrrolidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-7-methyl-6-[4-(piperidine-1-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-7-methyl-6-[4-(morpholine-4-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;6-[4-(Azetidine-1-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-7-methyl-3H-imidazo-[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(thiomorpholine-4-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-6-[4-(1-oxo-1I(4)-thiomorpholine-4-sulfonyl)-phenyl]-3H-imidazo[4,5-b]pyridine;6-[4-(1,1-Dioxo-1I(6)-thiomorpholine-4-sulfonyl)-phenyl]-2-[2-(4-methoxy-pyridin-2-yl)-ethyl]-3H-imidazo[4,5-b]pyridine;2-(4-{2-[2-(4-Methoxy-pyridin-2-yl)-ethyl]-3-H-imidazo[4,5-b]pyridin-6-yl}-benzenesulfonyl)-1,2,3,4-tetrahydro-isoquinoline,and the salts, N-oxides and the salts of the N-oxides thereof.
 34. Amethod for treating a disease or disorder in a patient comprisingadministering to said patient a therapeutically effective amount of acompound of formula I compound of formula I

in which R1 is hydrogen or 1-4C-alkyl, R2 is hydrogen or 1-4C-alkyl, andR3 is 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 is 3-7C-cycloalkyl,phenyl-1-4C-alkyl, hydroxy-2-4C-alkyl, 1-4C-alkoxy-2-4C-alkyl, phenyl,pyridyl, or R11- and/or R12-substituted phenyl, in which R11 is1-4C-alkyl, halogen, 1-4C-alkoxy, or mono- or di-1-4C-alkylamino, R12 is1-4C-alkyl or halogen, R2 is hydrogen, hydroxy-2-4C-alkyl,1-4C-alkoxy-2-4C-alkyl or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, or in which R1 and R2 together andwith inclusion of the nitrogen atom, to which they are bonded, form aheterocyclic ring Het, in which Het is a fully saturated or partiallyunsaturated mono- or fused bicyclic ring or ring system made up of afirst constituent being a 3- to 7-membered monocyclic fully saturatednon-aromatic heterocyclic ring B, which heterocyclic ring B comprisesone to three heteroatoms independently selected from the groupconsisting of nitrogen, oxygen and sulfur, and which heterocyclic ring Bis optionally substituted by one or two oxo groups, and, optionally,fused to said first constituent, a second constituent being a benzenering, and which ring Het is optionally substituted by R21 on a ringcarbon atom, and/or which ring Het is optionally substituted by R22 on afurther ring carbon atom, and/or which ring Het is optionallysubstituted by an ethylenedioxy group, and/or which ring Het isoptionally substituted by R23 on a ring nitrogen atom, in which R21 is1-4C-alkyl, 1-4C-alkoxy or phenylcarbonyl, R22 is 1-4C-alkyl or1-4C-alkoxy, R23 is 1-4C-alkyl, phenyl-1-4C-alkyl, 1-4C-alkylcarbonyl,1-4C-alkoxy-2-4C-alkyl, mono- or di-1-4C-alkylamino-2-4C-alkyl, phenyl,pyrimidyl, pyridyl, formyl, 3-7C-cycloalkyl, 3-7C-cycloalkylmethyl, orR231- and/or R232-substituted phenyl, in which R231 is halogen, cyano or1-4C-alkyl, R232 is halogen or 1-4C-alkyl, and R3 is hydrogen, halogen,1-4C-alkoxy, 1-4C-alkyl, trifluoromethyl, or completely or predominantlyfluorine-substituted 1-4C-alkoxy, and in which R4 is hydrogen, halogen,1-4C-alkyl or 1-4C-alkoxy, R5 is 1-4C-alkyl, A is 1-4C-alkylene, or asalt, N-oxide or a salt of an N-oxide thereof, wherein the disease ordisorder is selected from the group consisting of COPD, asthma,rheumatoid arthritis, osteoarthritis, neuropathic pain, Crohn's diseaseand ulcerative colitis.